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Reflections and Ways Forward

The workshop’s fourth session focused on optimizing the use of vaccines. Its objectives were to discuss the impact of vaccines in mitigating emerging threats during an outbreak, to discuss approaches to strengthen public trust in science and public health programs, and to synthesize priority actions that may ensure that immunization programs reach everyone. Nicole Lurie, strategic advisor to the chief executive officer at the Coalition for Epidemic Preparedness Innovations (CEPI), gave a plenary presentation of new vaccines in the midst of an outbreak. She discussed vaccination research, lessons learned from past outbreaks, regulation and safety monitoring, and the effects of coronavirus disease 2019 (COVID-19) on vaccine development and acceptance. Lurie’s plenary presentation was followed by a discussion moderated by Kent Kester of Sanofi Pasteur.

The session concluded with a panel on inoculating against misinformation and rebuilding the public’s trust in science, moderated by Alison Buttenheim from the University of Pennsylvania. The panelists included Sander van der Linden, director of the Cambridge Social Decision-Making Laboratory; Ethan Lindenberger, activist; and Kasisomayajula Viswanath, Lee Kum Kee Professor of Health Communication at the Harvard T.H. Chan School of Public Health. Van der Linden discussed his work on developing the Bad News Game, a psychological vaccine against misinformation. Lindenberger discussed the need to empathize with vaccine rejectors and anti-vaccine advocates. Viswanath explored issues related to the social science approach to fighting vaccine hesitancy. The panel was followed by visionary statements on priorities in building vaccine acceptance and uptake for the next generation from Peter Hotez, professor and dean of the National School of Tropi-

cal Medicine at the Baylor College of Medicine; Narenda Arora, executive director of Inclen Trust International; Monika Naus, medical director of the Communicable Diseases and Immunization Service at the British Columbia Centre for Disease Control, Canada; and Jean-Marc Olivé, an independent consultant formerly at the World Health Organization (WHO). The workshop concluded with closing remarks from Peter Daszak, chair of the Forum on Microbial Threats and president of EcoHealth Alliance.

NEW VACCINES IN THE MIDST OF AN OUTBREAK

Presented by Nicole Lurie, Coalition for Epidemic Preparedness Innovations

Lurie discussed the optimal use and vaccine confidence of a new vaccine during a global pandemic. Drawing on lessons learned from previous outbreaks, she suggested strategies for strengthening global solutions to vaccine financing, development, regulation, and distribution during epidemics and pandemics.

Collaborative Research to Respond to the COVID-19 Pandemic

Vaccines will likely be the strategy that ends the COVID-19 pandemic, said Lurie. She described the process of developing a vaccine during a pandemic as “building the plane as we are flying it,” emphasizing the difficulty of simultaneously developing vaccines and vaccination campaigns in the United States and around the world while also contending with the virus. Because there is not yet a strong vaccine candidate for COVID-19, vaccine confidence is being considered without the benefit of data on safety, efficacy, and characteristics. This dynamic poses a number of challenges to development, vaccination campaigns, and vaccine confidence, Lurie noted. In response, unprecedented global scientific collaboration is taking place in examining the disease, developing vaccines, and creating new platforms and technologies to manufacture the vaccines.

While it may seem as if all aspects of developing vaccines for this novel virus are new, the effort is actually building on many years of investments, said Lurie. This includes research on the human–animal interface and the kinds of diseases likely to affect humans, as well as how this knowledge can be applied to outbreak preparedness. Tremendous investment has been channeled into understanding the coronavirus, stemming in part from a recognition that severe acute respiratory syndrome (SARS) would eventually reemerge. In addition, investment has been made—particularly at the National Institutes of Health (NIH)—in researching prototype pathogens and the coronavirus to understand the role of the spike protein. Furthermore,

much investment and advancement in vaccine platform technologies have taken place over the past decade. These were built on the success of experience and research platforms, and they are enabling the work being carried out today, she added.

Lessons Learned from Past Outbreaks

Multiple lessons can be gleaned from the vaccine development efforts that stemmed from SARS (2003), influenza A virus subtype H1N1 (2009), Ebola virus disease (2014–2016), and Zika virus (2015) outbreaks, some of which were successful and some of which were incomplete.

Lessons from SARS (2003), Zika (2015), and Ebola Virus (2014–2016) Outbreaks

Lurie highlighted two lessons learned from the SARS, Zika, and Ebola outbreaks: getting an early start and seeing the process through to completion. In the case of both SARS and Zika, vaccine development efforts were well under way. However, the SARS outbreak ended before a vaccine was developed, and government funders and others lost interest in seeing vaccine development through to completion or to a later stage of advanced development. In the case of Zika, vaccines progressed quite far, but then the U.S. government—the primary funding source—deprioritized the effort. This has contributed to some reluctance on the part of major vaccine developers and manufacturers to begin working on a COVID-19 vaccine as soon as possible, Lurie noted. The Ebola outbreak illustrates the value of an early start, said Lurie. At the point when the outbreak had the potential to become a matter of major global concern, a vaccine candidate was already partially through the development process. Having the capability to accelerate the development of this existing candidate jump-started the creation of a vaccine, she added.

Lessons from the H1N1 Pandemic (2009)

Lurie also described several lessons learned from the development and deployment of vaccines in response to the 2009 H1N1 pandemic. The first is the value of what Lurie called “on-ramps.” The U.S. government has a framework for responding to novel pathogens, particularly influenza viruses, that involves beginning vaccine development—that is, taking an “on-ramp”—when a new strain appears. Development stops if it is determined that the pathogen does not merit further research. This may mean that development ceases after a seed strain is made or, in the case of H7N9, it may go all the way through the development process to the manufacturing and storage of bulk vaccine in case it is needed in the future. Lurie values this

approach of starting early, saying that in the midst of an outbreak one cannot make up for lost time, but one can always take an “off-ramp.” Thus, she argued that starting development early when new pathogens appear should be the default process. Development can then be stopped at whatever point it is clear that a vaccine is not needed. Early development requires that vaccine funders, especially the U.S. government but also funders from around the world, remain reliable partners to the vaccine industry, she maintained. Otherwise, industry partners feel abandoned and unwilling to risk beginning development as early the next time there is an outbreak.

The second lesson learned from the H1N1 pandemic was the value of speed, said Lurie. Efforts are under way to hasten the delivery of a COVID-19 vaccine, such as Operation Warp Speed and CEPI’s work to have vaccines manufactured before clinical trials are performed and it is known whether they work. Lurie explained these efforts are shaped by experiences with the pandemic H1N1 virus and expediting the process for influenza vaccines. Methods of making flu vaccines are well established, so it was possible to work off of earlier vaccine platforms to create an H1N1 vaccine for this strain. For instance, the U.S. Food and Drug Administration (FDA) generally agrees to license egg-based and cell-based vaccines for novel influenza vaccines as a strain change. Lurie said the current “Holy Grail” is to develop other platforms that are faster, more reliable, and pathogen-agnostic, which would enable new vaccines to be regulated as a pathogen changes. She added that the COVID-19 pandemic is providing experience with maturing platforms and ways to improve them.

Regulation and Safety Monitoring

It is important to consider regulatory alignment in planning for optimal use of and confidence in new vaccines from novel platforms while in the midst of an outbreak, said Lurie. Each country has its own regulatory system, and regulators are not always working together. In recent years, CEPI has made efforts to promote collaboration among regulators from around the world to discuss vaccines early and contribute scientific advice about how to move forward with vaccine development. During the COVID-19 outbreak, regulators have formed an international organization that includes FDA, the European Medicines Agency, Chinese regulators, regulators from African countries, and WHO.¹ In this forum, regulators have come together to share ideas about regulatory science, procedures for authorizing the use of vaccines, and approaches to vaccine manufacturing. Lurie said that if

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¹ More information about the COVID-19 response from the International Coalition of Medicines Regulatory Authorities is available at http://icmra.info/drupal/en/covid-19 (accessed February 19, 2021).

there are vaccine strains that some regulators authorize, but others do not, it could undermine vaccine confidence; this underscores the importance of continued collaboration among regulators. Such collaboration may provide a model for the future.

Safety monitoring is also critical for optimal vaccine uptake, said Lurie. In the United States, concerns have been raised about the premature authorization of a vaccine that has not adequately been tested from a safety and efficacy standpoint. Lurie said this concern is unfounded, because the vaccine development enterprise understands the importance of ensuring a vaccine’s safety and testing it on many thousands of people before it is authorized for use. This level of testing is necessary for both vaccine safety and vaccine confidence, because any mistake can (1) put all other vaccine candidates that are in development at risk and (2) undermine the already precarious level of confidence in the world’s entire vaccine system.

Lurie said that the most important safety work comes after a vaccine is released, whether this is post-emergency authorization or post-licensure. It is only at that point that vaccines are used in enough people to enable detection of rare adverse events that may be serious enough to merit halting the vaccine. She noted a number of advances in safety monitoring during the H1N1 pandemic, when the U.S. government used the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), and methods through which health care systems conduct their own surveillance for vaccine safety signals by using health information technology. Lurie suggested that given such developments, safety monitoring for a COVID-19 vaccine should be more robust than was possible a decade ago. Furthermore, she advised that continuous, clear, transparent information about adverse events following immunization be provided to the public, because there will be health events that happen by chance but are attributed to vaccines. Thus, maintaining vaccine confidence involves helping the public better understand efficacy data and safety monitoring to build confidence that vaccine information being shared is truthful.

Challenges and opportunities in vaccine development are intensified when dealing with a global pandemic, noted Lurie. She predicted that more than one COVID-19 vaccine will become available at roughly the same time. Furthermore, she anticipated that high-income countries with strong pharmacovigilance systems will likely initially receive the largest quantities of vaccine, which presents an opportunity for those countries to collaborate by using the same safety signal definitions and pooling their data to facilitate early detection of any adverse event signals. This would create a strong information base that could then be shared with countries that do not have strong pharmacovigilance systems, thus helping them strengthen their systems and understand where best to focus, while also remaining aware that they may detect different types of signals. Global collaboration on safety monitoring will be foundational for ensuring optimal uptake, vaccine confidence, and

responding to rumors and misinformation with solid, reliable, and verifiable information, Lurie said.

Coordinating COVID-19 Vaccine Development in the United States and Worldwide

Lurie noted contrasts between vaccine development in the United States and much of the rest of the world. The United States invests in systems for the basic science, surveillance, and advanced development of vaccines through the Biomedical Advanced Research and Development Authority. The U.S. Congress allocates funds for scaling up manufacturing and full-scale manufacturing; it also provides a financial guarantee to the companies that doses manufactured will be purchased. Systems developed through the U.S. Centers for Disease Control and Prevention (CDC) and in collaboration with state and local governments ultimately distribute the vaccine. Thus, the federal government provides end-to-end financing and has responsibility for pharmacovigilance systems.

Lurie said that prior to the point at which the U.S. government began backing development of a COVID-19 vaccine in earnest, CEPI examined the portfolio of vaccine candidates it had been developing before the outbreak. These included vaccine candidates for diseases that might have epidemic potential, including Middle East respiratory syndrome (MERS), and platform technologies that could be used in the event of Disease X.² Lurie noted that a host of pathogens, including Lassa, Nipah, MERS, and Disease X, are on the WHO priority list. Around January 7, 2020, just before the COVID-19 gene sequence was posted, CEPI reached out to the developers of the MERS vaccines and of the platform technologies and requested they pivot their efforts to COVID-19 as soon as the gene sequence was posted. CEPI had 2 weeks to determine how to provide these developers with the money they needed to get started. Over time, the U.S. government has invested many billions of dollars in vaccine development, while China has proceeded with its own vaccine development.

Prior to the COVID-19 pandemic, there was no global entity to enable vaccine development at the international level in the ways the United States does at the national level, such as:

• Funding phase 3 pivotal trials;
• Scaling up manufacturing capacity to produce large numbers of doses;

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² More information about prioritizing diseases for research and development in emergency contexts is available at https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts (accessed November 2, 2020).

• Making advance purchase commitments or advance market commitments to vaccine developers, which would eliminate their risk in manufacturing doses of vaccine that are not yet proven to work in clinical trials; or
• Buying vaccine and distributing it in an equitable fashion around the world.

Thus, these are all components of a global system outside of the United States that is being built during the current pandemic.

The Access to COVID Tools Accelerator (ACT Accelerator) was formed as a partnership among WHO, a number of other global organizations, and several companies. Within the ACT Accelerator, there is a vaccine pillar that is co-led by CEPI and Gavi, the Vaccine Alliance, and heavily involves WHO. Lurie said that through this partnership, the rest of the world has now created systems to finance the advanced development, scale up, and manufacture of vaccines. She added that fundraising has relied on the leadership of the European Commission. As of August 2020, CEPI, Gavi, and a host of countries were coming together to finalize agreements on how they will make advance commitments to purchase vaccines together as a large buyer coalition or as a combination of coalitions. Thereby, companies will be able to complete scale out of their vaccine or scale up of manufacturing. The manufacturing is being done with Operation Warp Speed in an effort to begin distribution around the world as soon as the trials are complete. Working with WHO, a global allocation framework is being developed to ensure that frontline workers and priority populations around the world are the first to be vaccinated. Lurie said all data and modeling indicate that vaccinating people around the world in prioritized tiers will end the pandemic and stimulate economic recovery faster than vaccinating all people in any one country.

COVID-19 Vaccine Acceptance

Global partners responsible for distributing vaccine and assisting with vaccine campaigns, especially in low-income countries, are planning and developing protocols to distribute and administer COVID-19 vaccines, said Lurie. Work is also under way around vaccine literacy, vaccine confidence, and putting systems in place to understand people’s concerns and current confidence in vaccines. Lurie said that on a country-by-country and a population-by-population basis, professionals need to use everything they have learned to optimize vaccine acceptance as soon as a safe and effective vaccine is available in order to end the pandemic. This is a challenging situation, because many low-income countries have substantial morbidity and mortality from other infectious diseases. Therefore, while some countries have high enthusiasm for a global vaccination system, others have notable

hesitancy. Lurie said that CEPI is receiving questions such as “What do you do when people are more afraid of the vaccine than the disease?” While more challenges undoubtedly lie ahead, everything that can be accomplished collaboratively as a global community will set the stage for bigger, better, and faster responses in the future, said Lurie. Lurie’s hope is that in addition to scientific and regulatory collaboration spearheaded by NIH and FDA, collaboration is also ongoing regarding vaccine development and shared financing. When it comes to making vaccines available to the world, “none of us are safe until all of us are safe,” said Lurie.

Discussion

Sustainable Global Vaccine Collaboration

Given that pandemics are episodic in nature, Kester asked how truly global solutions that are equitable and well received can be sustained in a context of events that only rarely occur. In the case of Zika, interest in a vaccine evaporated as the threat lessened. He asked how CEPI, Gavi, and others can facilitate sustainable global solutions. Lurie responded that once a vaccine is started, a commitment is needed that the vaccine will be taken to a stage of development where it can be brought forward rapidly in the future if need be—this should have been done with Zika. If COVID-19 happens to disappear before a safe and effective vaccine is developed, vaccines should continue to be moved through development and a certain amount stockpiled to enable rapid response when the virus reemerges, she said.

Additionally, the COVID-19 pandemic has highlighted the need for global financing and financial preparedness. “You can’t be passing a tin cup in the middle of a pandemic,” Lurie emphasized. Once this pandemic is under control, Lurie advised global payers to come together to determine how to finance the response to a future pandemic. Regardless of the global financing system and state of financial reserves, it should be expected that a certain amount of money will be spent each year as the cost of preparedness. A system is needed in which whenever a new pathogen emerges, researchers agree to take an “on-ramp” and perform the enabling science work to determine whether a vaccine is required, then continue to perfect platforms and begin vaccine development. This keeps researchers practiced and keeps products moving forward. Funding these “on-ramps” of vaccine development should be the cost of preparedness, Lurie asserted. Even if this cost is $10 million or even $50 million per year, it pales in comparison to the $350 billion in gross domestic product that is currently being lost each month because of the pandemic, she said. Currently, financing preparedness seems to be an issue even bigger than scientific preparedness and, moving forward,

it is one that must be solved by the world collectively, Lurie said. She added that being prepared is fair to companies, developers, the scientific community, and to the public. This approach could be characterized as an insurance policy in paying premiums to avoid larger issues later on, added Kester.

Lessons Learned from Ebola for Vaccine Confidence

Kester asked whether there are learnings, case studies, testimonials, or other insights—aside from what has been published—about the early use of the Ebola vaccine in health workers that can be adapted for building confidence more broadly. Lurie said the Ebola experience helped scientists realize that many people do not really understand the concept of a vaccine and what it is. Furthermore, they learned that it is possible to sit with trusted community leaders and explain how vaccines work, enabling these leaders to explain this to their communities in turn. Lurie said that fundamentally and in all parts of the world, confidence building comes from trusted community leaders understanding the vaccine process and communicating information to their populations. Lurie highlighted the practices of the United Nations Children’s Fund (UNICEF) and Médecins Sans Frontières, who took “the pulse of populations” about the Ebola outbreak and vaccine, then disseminated what they learned. This included establishing listening posts, monitoring social media in areas affected by the Ebola outbreak, and talking to people on the ground about their beliefs and what they were hearing in their communities. She said these practices were essential to the explanation and acceptance of vaccines.

To exemplify the importance and power of good science, randomized controlled trials (RCTs), and communication, Lurie shared a story of a meeting with the Secretary of the U.S. Department of Health and Human Services, NIH colleagues, and the president of Liberia. The president said that her people were reporting that the vaccine was making people go blind. This revealed that better communication was needed about how vaccines work, how Ebola affects people, and how RCTs operate. The researchers explained that it was Ebola that was causing blindness, not the vaccine. The group detailed how the RCT was set up, explaining that it was actually people in the control or placebo group who were going blind, not those who had received the vaccine. This illustrates how knowledge gaps can be bridged by helping people understand how clinical trials are designed and creating listening opportunities. She noted that every country, culture, and language will have a slightly different way of approaching this information. Therefore, anthropologists on the ground should work with communities and collect information specific to each setting. Lurie added that WHO’s approach is to send anthropologists anywhere they send epidemiologists.

Vaccine Deployment in Countries Lacking Infrastructure

Noting that financing the development, manufacturing, and deployment of vaccines has already been discussed, Kester asked how low- and middle-income countries (LMICs) with limited infrastructure could deploy the COVID-19 vaccine and adequately vaccinate their populations. Lurie suggested building on existing systems rather than trying to start from scratch. For instance, most LMICs currently have childhood vaccination programs, and the childhood vaccination rates in these countries are often higher than in the United States because of the supply chains created with support from Gavi, UNICEF, and nongovernmental organizations. Acknowledging that the system is not perfect, Lurie added that if the COVID-19 vaccine ends up requiring a –80 degrees Celsius cold chain, it is likely that only the handful of countries with this capacity as a legacy of the Ebola vaccine campaign will have that capability for the foreseeable future. Thus, planning is already under way to provide countries with technical assistance.

The H1N1 pandemic experience revealed gaps in preparedness planning, noted Lurie. During that outbreak, the United States shared a percentage of its vaccines with WHO to distribute around the world. However, many countries were not prepared to accept it nor had developed plans in place to use it. A series of planning and preparedness checklists were developed to help countries develop the logistics for their vaccination campaigns. Many LMICs receive vaccines that are paid for by Gavi; many also receive funding from the World Bank that can be used to hire staff and develop vaccine plans and campaigns. This will help build on these countries’ strengths and increase their capacity moving forward, she said.

Vaccine Adverse Events

Kester noted the variety of systems in the United States and other countries for recording adverse events. With self-reporting, as used by the VAERS system, reports are not curated, and people can report medical information that may not be germane. Given the difficulty in differentiating true vaccine adverse events and events that are unrelated to vaccines, Kester asked about the strategies to instill vaccine confidence. Lurie noted that unrelated medical events are frequently attributed to vaccines by the public, such as people believing they got seasonal influenza from the vaccine. In addressing H1N1, extensive work was performed in establishing background rates of events such as Guillain-Barré syndrome, developing clear case definitions of events that might be vaccine adverse events, and then establishing background rates. Lurie said the same process needs to happen for COVID-19. She noted that CEPI has worked with the Brighton Collaboration to look at particular

types of adverse events that might be unique to COVID-19 vaccines,³ particularly in terms of either antibody-dependent enhancement or lung pathology, and then develop and disseminate those definitions. Ideally, countries would determine to use and develop a harmonized set of definitions for potential adverse events, and then commence work to understand the background rates now, before a vaccine is available. This enables the comparison of the rates of reported adverse events with normal expected background rates to determine if rates are actually increasing with the vaccine. Lurie acknowledged that communicating with the public about this is a challenge. Medical events will happen that are completely unrelated to vaccines, yet people will attribute them to the vaccine and amplify those putative associations on social media and other channels—some of which is maliciously intended. She emphasized that in addition to back-end work to maintain public confidence, front-end work is also needed to establish background rates, help people understand what they are, disseminate them, and standardize definitions. In this way, the strengths of systems in higher-income countries can be used to generate information that can be shared worldwide.

Addressing Potential COVID-19 Vaccine Failures

Given the regional, national, and global deployment needed for a COVID-19 vaccine, Kester asked about the best approach for detecting vaccine failures. In a clinical trial, the population tested is selected with demographics, ages, and medical conditions in mind. However, a global vaccine will presumably be given to all people at some point, and some failures are to be expected, as even good vaccines do not work in everyone. He asked how the strengths and weaknesses of a particular vaccine can be communicated accurately when so much misinformation is instantaneously amplified by social media. Lurie replied that this challenge will be compounded if multiple vaccines are in the field simultaneously, because the first wave of vaccines will likely have efficacy well below 100 percent. Some may even have efficacy closer to the seasonal influenza vaccine (around 50 percent). Thus, there will be breakthrough infections and failures.⁴ Researchers will need to understand whether those breakthrough infections are typical cases of COVID-19 or if they are associated with additional adverse events.

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³ More information about the Brighton Collaboration is available at https://brightoncollaboration.us (accessed November 2, 2020).

⁴ According to the CDC definition, breakthrough infection refers to “development of a disease despite a person’s having responded to a vaccine.” See https://www.cdc.gov/vaccines/terms/glossary.html#b (accessed February 19, 2021).

Lurie emphasized there is no entity in the global system that is responsible for conducting or funding phase 4 (ongoing safety monitoring) studies, the burden of which will be enormous. Although there are study designs for determining failure rates, they require the ability to collect data. However, this is more easily accomplished in organized health systems where information about receipt of a vaccine can be linked to information about hospitalization or office visits for COVID-19 treatment. Countries with this level of capacity will likely need to bear the initial burden of this work, she added.

INOCULATING AGAINST MISINFORMATION AND REBUILDING THE PUBLIC’S TRUST IN SCIENCE

Panel Discussion

A Psychological Vaccine Against Misinformation

Van der Linden described the psychological vaccine technique for curbing the impacts of misinformation. Just as weakened doses of a pathogen can be injected into the human body to trigger the production of antibodies and confer resistance against infection, psychological “inoculation” exposes individuals to weakened doses of misinformation, fake news, and other techniques of deception about vaccination to create “mental antibodies”—that is, to trigger a psychological process of resisting and arguing against these deceptive techniques.

Psychological Inoculation Against Misinformation

Van der Linden explained how psychological inoculation is analogous to biological inoculation, where a psychological “vaccine” can trigger “mental antibodies” against misinformation. The psychological vaccine has both an affective basis and a cognitive basis. Recipients are warned of the impending threat to their belief systems, such as the threat of fake news; this is the affective basis. In addition, they are given preemptive refutation of harmful content. This cognitive basis has been termed “prebunking.” As opposed to debunking and fact checking, prebunking gives individuals the needed cognitive tools in advance of their exposure to harmful content. This aspect of psychological inoculation makes the analogy to physical inoculation quite apt, he said. Exposure to these psychological vaccines triggers mental antibodies that, through internal rehearsal, can increase individuals’ resistance to future exposure and persuasion attempts, thus achieving psychological inoculation. Studies have been conducted to investigate the mechanisms of these psychological processes (Cook et al., 2017), but the primary purpose of this approach is to scale up and create “heard immunity” against misinformation.

Bad News Game

The Bad News Game immerses players in a simulated social media environment, putting them in the role of a fake news producer (Vaidyanathan, 2020). Designed to expose the tricks used by fake news creators, this approach is similar to revealing how a magician’s trick is performed, said van der Linden. While a person might initially be fooled by fake news, two potential approaches can expose the trick: (1) interveners can present relevant education and scientific information that refutes the fake news or (2) interveners can show how the trick is done and let the person perform the trick themselves. The latter, which he described as a more powerful experience, is the approach used in the Bad News Game to teach people about fake news.

Van der Linden explained how the Bad News Game works. The game’s interface includes a follower count, which tracks the player’s number of in-game social media followers, and a credibility meter. A narrator presents the player with options at each stage. These features guide the player’s choices toward balancing the incentives of growing a following while maintaining some credibility. The objective of the game is to get as many followers as possible. The game offers badges for polarization, impersonation, conspiracy, trolling, emotion, and discredit. These badges are informed by the game designers’ review of available literature, which revealed that these six techniques are used with great frequency. The game’s first lesson is an online impersonation. Players begin by impersonating Donald Trump with a tweet stating, “After long deliberation with my generals I’ve decided to declare war on North Korea. #KimJungDone.” Van der Linden presented an example of a simulated tweet designed to create an in-game echo chamber: “The Mainstream Media is one massive conspiracy. #FakeNews.” Because the game is hosted online, it can be updated based on current events. For example, as the COVID-19 pandemic unfolded, new elements were added to the game. Official WHO tweets were added, and the game demonstrated how fake news promoters responded to real WHO tweets in an attack on WHO’s official statement. A trolling tweet was added to the game that accuses WHO of conspiring to release the virus as a bioweapon. Aimed at a younger audience, the game is intended to be a humorous, sharable conversation starter. The inoculating effect of the game is represented with a badge system. As it is impossible to inoculate individuals against every instance of fake news, the game targets the underlying mechanisms of fake news so players can learn to identify them. The in-game badges are intended to reveal these underlying mechanisms of fake news.

Findings from Bad News Game Research

Before and after playing the Bad News Game, players are tested on their ability to spot misinformation techniques. Thus far, the game has collected

data from more than 15,000 people who have played the game. The first study conducted with this data found that playing the Bad News Game did not change the credibility ratings players gave for real news. In contrast, players rated fake news items containing techniques revealed in the game as being less credible (Roozenbeek and van der Linden, 2019). The effectiveness of the game was not associated with the age or political affiliation of players; playing the game resulted in a shift in ability to spot misinformation techniques. Since the initial study, RCTs have been conducted to evaluate the game, including opt-in experiments. One study found the same effect among 197 participants (Basol et al., 2020). In this study, players were not only better able to spot misinformation techniques after playing the game, they were also more confident in their ability to correctly identify fake news.

Another study evaluated the long-term effectiveness of inoculation against misinformation among 150 participants (Maertens et al., 2020). Unlike a real vaccine, psychological inoculation cannot confer lifelong immunity to misinformation.⁵ However, the effects of psychological inoculation have been shown to persist for up to 2 months. Van der Linden and his colleagues are beginning to experiment with “booster shots” by having players revisit the game to remain alert and able to spot misinformation techniques. In partnership with the United Kingdom and the Harvard Kennedy School Misinformation Review, the Bad News Game was translated into several languages and tested cross-culturally with players from around the world.⁶

In conclusion, van der Linden invoked the words of Severus Snape, a character from the Harry Potter series, who said that one’s “defenses must be as flexible and inventive as the arts you seek to undo” (Rowling, 2014). Especially relevant in the context of addressing misinformation, this quote applies to the new, innovative, and adaptive solutions that are needed to supplement debunking and fact checking. Van der Linden made the point that at this point he can basically predict what types of misinformation will emerge for a given topic, which then provides the ability to preemptively provide individuals with good information before exposure to misinformation, and inoculating against techniques of disinformation are examples of such innovative solutions. Constant efforts to retroactively undo the damage of misinformation and reduce vaccine hesitancy include applying these approaches to new contexts as they emerge. Van der Linden advocated for preemptive efforts to prepare the public for the release of forthcoming COVID-19 vaccines. Efforts

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⁵ Van der Linden explained that this experiment had players in the control group play Tetris (Maertens et al., 2020).

⁶ More information about the work done on the Bad News Game by the Harvard Kennedy School Misinformation Review is available at https://misinforeview.hks.harvard.edu/article/global-vaccination-badnews (accessed October 15, 2020).

are under way to create new games similar to the Bad News Game that specifically address issues such as COVID-19 vaccine hesitancy and COVID-19 conspiracies. The aim of these efforts is to prebunk disinformation agents and to work toward psychological herd immunity.

Empathizing with Vaccine Rejectors and Anti-Vaccine Advocates

Lindenberger shared reflections from his vaccine advocacy work and insights from his personal experience being raised by his mother, who rejected vaccines and chose not to have Lindenberger immunized as a child. He applauded the work presented by van der Linden, highlighting the importance of prebunking against misinformation and conspiracy theories of all kinds. At the age of 18, Lindenberger chose to catch up on his immunizations and began exploring the factors that lead individuals to reject vaccination. His work emphasizes the factors that lead certain people to be more susceptible to vaccine misinformation, aiming to humanize vaccine rejectors and acknowledge that many vaccine rejectors have good intentions. He explained that his experiences with misinformation have been rooted in how individuals interact with social media, along with other factors that can influence a person’s exposure and reaction to misinformation. Demographic factors such as age, gender, geographic location, or education may influence the way individuals engage with and respond to misinformation. For instance, Lindenberger’s mother had multiple children and did not attend college. Lindenberg suggested that these factors likely contributed to his mother’s likelihood to accept anti-vaccine misinformation. Additionally, he asserted that his mother’s strong maternal instincts made her susceptible to the misinformation tactics used to promote anti-vaccine information, as these often make strong emotional appeals to parents about the risks of child vaccination. He said his mother’s underlying acceptance of vaccine misinformation was eventually bolstered and galvanized by her exposure to anti-vaccine misinformation on social media, and he questioned whether she may ever change her mind about vaccines. Acknowledging that powerful actors aim to promote misinformation for reasons such as monetary and societal incentives, Lindenberger said vaccine advocates should take care to be empathetic and humanize those who accept misinformation, even while combating misinformation itself.

Buttenheim asked how Lindenberger’s mother might respond to the Bad News Game. Lindenberger explained that he has discussed misinformation similar to the content of the Bad News Game with his mother. For example, she has presented him with anti-vaccination videos that she found compelling in spite of containing no evidence and being full of misinformation tactics. He expressed frustration in seeing the apparent misinformation in these videos, but realized his mother was drawn to the emotional content they

contained. Rather than analyzing the video’s claims, his mother responded to the revelatory and world-breaking tone and presentation of the video. His attempts to refute misinformation claims have proven ineffective with his mother, and he speculated that, as with many diseases, preventing the spread of misinformation may be far more effective that trying to “cure” misinformation. This is especially true of polarizing issues, which make it difficult for debunkers to “reach across the aisle” once misinformation creates a divide. He compared this real-life experience to the in-game experience of playing the Bad News Game and concluded that education is key for addressing misinformation.

A Social Science Approach to Fighting Vaccine Hesitancy

Considering the personal experience and the gamified approaches to curbing misinformation presented by the panelists, Buttenheim asked how these might be folded into evidence-based campaigns to promote vaccination, especially for the COVID-19 vaccines. Viswanath said that addressing this question requires a clear understanding of the audience and the vaccine in question, adding that it is only a relatively small, although vocal, group that is fully committed to the anti-vaccine perspective. As Lindenberger described, once a person has been convinced by anti-vaccination information, they become resistant to logical arguments. Those extreme cases aside, Viswanath recommended that vaccine advocates direct efforts toward promoting childhood vaccination with skeptical parents—that is, those who are on the spectrum of vaccine hesitancy but are not yet committed to an anti-vaccination perspective. He said that the vaccine advocacy community has become the victim of its own success; as the prevalence of classic infectious diseases has decreased through vaccination, so too has visibility of these diseases. Thus, successful vaccination efforts have reduced both the perceived severity of vaccine-preventable diseases and the perceived susceptibility risk of becoming infected with these diseases. Addressing this gap between perceptions and reality is difficult. Typically, statistics have been used to communicate about the severity and susceptibility associated with these diseases, but statistics are not effective for most people. Viswanath acknowledged that even he, a social scientist, finds it difficult to process these kinds of statistics.

Preliminary findings from an ongoing survey-based study revealed that nearly 50 percent of respondents said that statistical information would not influence their medical decision making.⁷ Negative emotions are especially powerful in the decision-making process, as they can focus individuals’ attention on a small set of features and are easy to retrieve, reinforcing

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⁷ This preliminary finding confirms that medical decisions are influenced by emotions, an effect often called the “affect heuristic.”

their impact. Anti-vaccine content can easily use the effect of negative emotions. Therefore, the challenge of promoting vaccination should be tackled emotionally, said Viswanath. By recognizing that sharing facts and statistics about adverse events is unlikely to be effective, social scientists could approach vaccine hesitancy in a way that accounts for the emotional basis for decision making. Additionally, certain ethnic groups, such as African Americans, have a history of traumatic experiences with the scientific community, and this difficult history poses a challenge to vaccine advocates.

Viswanath cited survey data suggesting that 60–70 percent of individuals would be willing to get a COVID-19 vaccine once one becomes available. However, nearly 60 percent of surveyed individuals believe they are not susceptible to COVID-19 and 63 percent of individuals believe that they would not have a severe case should they become infected. Considering the abundance of misinformation and disinformation, communications strategies explicitly addressing the issues of susceptibility and severity should be used to promote compliance with public health measures. In conclusion, Viswanath reiterated the importance of identifying the audience and goals of communication campaigns, noting a distinction between campaigns promoting vaccination and campaigns promoting support of vaccination within social circles. He suggested that these campaigns employ aggressive, evidence-based tactics, such as the approaches that have been discussed throughout the workshop.

Using Data Versus Experience to Combat Misinformation Tactics

Buttenheim asked how the affect heuristic informed the design of the Bad News Game and what is known about how the specific emotional responses to disinformation differ from the responses to data. Van der Linden reiterated that presenting vaccine-hesitant individuals with data is inadequate for overcoming the emotional stories at play in their minds. Again, this points to the role of emotions in human judgment and decision making. Judgments are largely driven by experiential factors, and the affect heuristic greatly impacts the experiential system. Thus, people are primarily “experiencers,” learning through experiences. Elucidating this, he invoked the words of Mark Twain, who wrote:

In other words, a person who carries a cat by the tail learns something they could not have learned in another way. This illustration highlights that

experience is one of the most powerful mechanisms through which individuals learn about the world, and this can include vicarious experience, such as hearing about the bad experiences of others. The Bad News Game is intended to account for these insights and reveal the mechanisms of misinformation tactics to the players. Rather than countering false beliefs with truth, the game aims to make players aware of the tactics of misinformation that are often used to establish false beliefs. Thereby, the game can reveal to the player the ways in which they might be manipulated, potentially prompting them to reevaluate beliefs established through such manipulation. He emphasized that individuals are generally not receptive to approaches that directly target false beliefs.

Another aim of the Bad News Game is to provide a nonjudgmental environment in which players can make their own conclusions.⁸ He identified three aspects of the Bad News Game designed to achieve this. First, the messages and subjects of misinformation used within the game do not support a particular ideological message. Rather, the game allows the player to choose the subjects of misinformation used within the game, such as mocking large pharmaceutical companies or attacking the government. Allowing players to choose their own path within the game helps to lower their defenses, as players must have an attitude of openness in order for the inoculating effect of the game to be realized. Second, the game makes use of humor, including self-deprecating humor. This approach helps to diffuse the tensions that may be created by the players’ perceptions of elitism, awareness that the game is intended to be educational, or from the way the game mirrors the experience of social media. Lastly, the game engages players at an experiential level. Rather than targeting players’ cognition with facts, the game offers an interactive, visual experience in which players compose tweets and respond to other people, and allows them to learn through doing. This approach is more aligned with the natural learning process than the use of didactic content, said van der Linden. While individuals are capable of absorbing information from reading books or attending school, people learn to navigate the world by doing. The Bad News Game uses this insight and allows players to see how they can be manipulated through firsthand experience. Because these in-game experiences are directly related to concepts, experiences, and feelings they encounter throughout their lives, players are likely to heed the lessons of the Bad News Game. He clarified, however, that the game is not directly aimed at changing players’ behaviors, and it cannot be claimed that the game has increased vaccine uptake. The game is intended to be a tool that increases awareness of misinformation and the ways in which individuals can be misled.

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⁸ Van der Linden acknowledged that, while the game allows players to draw their own conclusions, it is designed to steer the players toward a particular set of conclusions.

Van der Linden remarked that his mother, like Lindenberger’s, sends him online content that may be questionable. Van der Linden proposed there may be a generational element to this shared experience. In such cases, people are more receptive to a discussion of the motivations and techniques of such content than an attack on the claims made within such content. Once someone has an inkling that a piece of content has an agenda to trick or misinform the audience, they are less likely to be convinced by that content. Buttenheim commented that the experience of a family member or colleague pointing out how one has been deceived may be just as unpleasant as being confronted with facts that refute false beliefs, although this coming from a trusted source may make a difference. Van der Linden agreed that trusted sources, such as family members and other in-group individuals, have more leverage to reveal misinformation. Nonconfrontational and nonjudgmental communication are best suited to revealing and combating misinformation techniques. For example, the Bad News Game was designed to be a nonjudgmental vehicle, and it uses humor to diffuse players’ potential feelings of threat. The game seems to be effective, but it may be less effective for those committed to an anti-vaccination perspective or those who do not frequently use the Internet or access information from multiple sources.

For those who will not play the Bad News Game, other methods may be used to inoculate individuals against misinformation techniques. One such method is being developed in collaboration with Google and involves short, animated videos that can be played before videos containing dubious claims. If such tools are unavailable, individuals may have to serve as nonjudgmental vehicles, engaging in a nonthreatening way to help reveal misinformation tactics to others. It may be difficult to engage without escalating, especially if individuals disagree about the subject of the misinformation. Van der Linden suggested avoiding talking down to others or making them feel unintelligent or uninformed. He also suggested the use of the Socratic method, asking questions to lead the person toward realization. These questions may include: “What is the source of the information?” and “Do you think the creator of this information may have ulterior motives?” He said that if a person answers “no” to the latter question, one might point out an affiliation between the creator of the content in question and a company to which they may be associated. If engaged in real conversation without insult, this kind of discourse may lead a person to recognize that they have been misled.

Persuasion Along the Spectrum of Hesitancy

Lindenberger highlighted the distinction between anti-vaccination advocates and those who are vaccine hesitant. The former is a small group who may be among the most difficult to reach with techniques aimed at

combating misinformation. Vaccine-hesitant individuals make up a much larger group and are more likely to be reached with such techniques. Furthermore, vaccine hesitancy is a greater threat to public health than anti-vaccination advocates, he asserted, pointing to vaccine hesitancy’s inclusion as one of the top 10 threats to global health WHO identified in 2019.⁹ Lindenberger noted that vaccine hesitancy is a greater concern than fringe groups promoting radical and often conspiratorial anti-vaccination information, and these radical ideas are not the most compelling reasons for vaccine hesitancy. He believes that vaccine-hesitant individuals are more likely to have been affected by less radical ideas, such as safety concerns, questions about vaccine effectiveness, and the desire to delay or skip specific vaccines. It is these less radical, more widely held ideas that vaccination advocates should target. Fortunately, Lindenberger surmised, vaccine-hesitant individuals, who tend to have fewer radical ideas about vaccination, may be easier to reach through the techniques discussed throughout the panel than anti-vaccine advocates. As many vaccine-hesitant individuals have a sense of uncertainty, they may be receptive to questions about the sources of claims, corrections about misinformation, and other conversations about vaccination. However, there are some individuals who will never be receptive to such techniques, and vaccine advocates should consider whether the individuals they discuss vaccination with are open to having their minds changed, he said.

Van der Linden agreed, adding that individuals fall somewhere along a spectrum of vaccine hesitancy. Some are susceptible to intervention but will revert to hesitancy while others are “immune to persuasion”—that is, they will never allow themselves to be convinced. The Bad News Game is not capable of convincing those who are immune to persuasion, he said, pointing out that even the metaphor of a vaccination against misinformation may be offensive to some individuals. Some individuals simply will not be reached, but working to protect individuals from becoming vaccine hesitant remains a worthy pursuit and can target those who are hesitant but still undecided. Van der Linden has found that, similar to experimental therapeutic vaccines, the Bad News Game has some therapeutic effects and can make players less extreme in their misinformation beliefs, that is, rather than abandoning their beliefs in misinformation, they have become more reflective about their beliefs. This suggests that those who have already been exposed to misinformation can benefit retroactively from vaccination against misinformation.

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⁹ More information about WHO’s top 10 global health threats in 2019 is available at https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 (accessed October 19, 2020).

Potential Risks of Revealing Misinformation Tactics

Buttenheim asked whether there may be risks associated with revealing the tricks of misinformation tactics. For instance, might the Bad News Game inadvertently teach misinformation agents how to create better misinformation? Van der Linden said that this is among the frequently asked questions about the Bad News Game, and that the game was carefully designed to avoid actually fooling players into believing in-game misinformation. Much time was spent pretesting the game’s content, ensuring that the humor was appropriate and that the game’s content was too ridiculous for players to actually believe. He contended the techniques exposed in the game are already being used by misinformation actors, such as those working in Russian troll farms. These misinformation actors are already aware of the techniques revealed in the Bad News Game, and they do not need to play the game to learn techniques of misinformation. He explained that there are two motives for spreading fake news: political motives and financial motives. The Bad News Game avoids incentivizing the players via these motives, and there is no financial or political aspect of the game’s design. These design decisions were made in hopes of preventing players from seeing the lessons of the game as aligned with their financial or political motives.

Van der Linden acknowledged the possibility that some small number of players could take the lessons of the game and apply them in a way that was not intended. The game’s developers worked to test whether this was happening. After the game went viral on Reddit, developers analyzed Reddit discussions for mentions of the game to learn what the players were saying about it. Conversations about the game reflected both positive feelings and some fears about the game. However, no conversations were found in which players discussed how the game’s lessons could be used to spread fake news. He compared this concern to the adage that “teaching someone a joke does not make them a comedian,” suggesting that teaching someone about misinformation tactics does not make them a misinformation agent. Similar concerns exist about meta-inoculation—that is, tactics that inoculate individuals against the effects of inoculation against misinformation—and his team is considering preemptive steps to address them, said van der Linden.

Viswanath pointed out there are various types of audiences. Many individuals do not use the Internet or do not play games on the Internet. A more nuanced view is needed to understand the spread of misinformation and how it affects social media users. If those exposed to misinformation via social media can be identified, then the tools discussed throughout this panel can be used to counter that misinformation. He pointed out that while there is much public discourse on the impact of social media, social media is not a major source of news per se. Rather, social media plays a role in reinforcing and amplifying messages that may begin in more obscure areas

of the Internet. He added that developing tools to address these amplifying effects, being aware that these tools can be a way to mainstream dis- and misinformation, and reaching those who are not engaged in social media are areas of focus moving forward.

Social Media’s Impact on Misinformation and the Role of Storytelling

Buttenheim remarked that as the COVID-19 pandemic unfolded, there was much discussion of “info-demiology,” that is, who is hearing and absorbing what information, and how information is spreading. She considered the possibility of examining patients’ “social mediome,” gauging the extent to which a person gets their news from social media, as part of clinical encounters. Such investigations may help vaccination advocates tailor clinical counseling to the ideas and preconceptions of individual patients. Lindenberger reported that some of the factors influencing misinformation are able to be identified by the platform operators themselves, and recent improvements have been made in the ways social media platforms handle misinformation. These changes are relevant for mitigating the potential effects of rapid sharing and spreading of singular sources of misinformation. Furthermore, platforms such as Twitter, YouTube, and Google have been effective in minimizing the spread of certain misinformation. For instance, YouTube has de-ranked or not recommended certain videos containing misinformation, Twitter has disallowed the use of certain hashtags used to spread anti-vaccination misinformation, and Facebook does not recommend anti-vaccine groups to those not already subscribing to anti-vaccination content.

Informed by his experience with his mother, who was greatly influenced by stories, anecdotes, and testimonials, Lindenberger explained that education and storytelling are his areas of focus. Personal experiences were more compelling to his mother than the data and statistics presented by the scientific community, and this contrast likely contributed to her eventual rejection of the truth of scientific information. Numbers do not resonate with people; people resonate with people, he said. Stories, drawing on imagery and personal experiences, are a highly effective method often used throughout history in human communication. The scientific community may be undervaluing anecdotes, as anecdotes are sometimes necessary to provide a real sense that what scientists know actually happens. For instance, stories about individuals who have lost limbs to meningitis or lost family members to measles can be used in a powerful way to combat misinformation. Lindenberger explained he has chosen to study journalism in order to pursue this approach in his work.

VISIONARY STATEMENTS ON PRIORITIES IN BUILDING VACCINE ACCEPTANCE AND UPTAKE FOR THE NEXT GENERATION

Poverty, Anti-Science, and COVID-19

Presented by Peter Hotez, Baylor College of Medicine

Hotez referenced his upcoming book, Preventing the Next Pandemic: Vaccine Diplomacy in a Time of Anti-Science, as the basis for his visionary statement (Hotez, in press). In it, he makes the case that enormous progress has been made in vaccinating the world’s children and in producing adult vaccines, attributable in large part to the work of Gavi, WHO, and UNICEF. However, Hotez asserted that over the past few years, there has been a slowing, a halting, and in some cases even a reversal of some of those global health gains. He attributed this to a constellation of social determinants, including war and political collapse, instability, urbanization, deforestation, climate change, and a rise in anti-science. Hotez identified hot spot areas which, on the surface, may not seem to have much in common: Texas and the U.S. Gulf Coast; Central Latin America; Africa; the Arabian Peninsula; and China and the Philippines. These areas are all seeing slowing or reversing of vaccination gains. Simultaneously, an unexpected level of poverty-related diseases is affecting G20 nations, said Hotez. An examination of the total number of cases of poverty-related diseases, such as leishmaniasis, Chagas disease, dengue, and tuberculosis, revealed that these are overwhelmingly infecting poor people living among the wealthy in G20 countries. Hotez mentioned that a book he recently published, Poverty and the Impact of COVID-19, details how COVID-19 is operating along those same principles (Hotez, 2020b); those disproportionately affected by COVID-19 include poor people living in Brazil, India, and the United States. In the United States, a significant disparity in COVID-19 cases has disproportionately impacted African American and Latino communities, particularly in Texas and in the southern United States.

Hotez said that in the midst of the pandemic, one might intuit that eagerness for a COVID-19 vaccine would lead to a retreat of the anti-vaccine movement. Instead, the movement has gained strength during the pandemic, he maintained (Hotez, 2020a).¹⁰ Hotez stated that he has been confronting the anti-vaccine movement for years, responding to their false claims that vaccines cause autism and other chronic illnesses by writing a book about his daughter with autism, Vaccines Did Not Cause Rachel’s Autism (Hotez, 2018). During the pandemic, the anti-vaccine movement has made

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¹⁰ More information about the effects of the COVID-19 pandemic on routine pediatric vaccine ordering and administration is available at https://www.cdc.gov/mmwr/volumes/69/wr/mm6919e2.htm (accessed November 5, 2020).

allegations against Operation Warp Speed, saying that COVID-19 vaccines are rushed, they are not adequately tested for safety, they are influenced by conflicts of interest between pharmaceutical companies and the U.S. government, and they conflict with what the movement calls an individual’s “health freedom.” Hotez contended that despite these allegations being untrue, the lack of messaging from the White House and Operation Warp Speed has enabled anti-vaccine groups, who are now expanding their remit to campaign against masks and contact tracing. Although substantial progress is being made on vaccines, Hotez said that an epic struggle is on the horizon. On one hand, he anticipates there will be multiple COVID-19 vaccines coming out in 2021, including a new recombinant vaccine for COVID-19 that is currently in accelerated production in India with Biological E, Ltd. (Hyderabad, India).¹¹ On the other hand, the aggressive forces of poverty, climate change, war, political collapse, urbanization, and anti-science must be countered.

Vaccine Myths, Religion, and Declining Coverage Rates in India and Indonesia

Presented by Narendra Arora, Inclen

Arora recalled that in 1997, still the early days of polio eradication in India, the vaccination program was just being rolled out. During a nationwide evaluation of the program at that time, Arora found a cluster of 20–25 homes in a small district of southern India who were refusing to take the vaccine. This community, a religious group, cited concerns about the polio vaccine causing sterility. Arora said this information was shared with the system, but not much attention was given to the matter. However, within the following 4 or 5 years, it became clear this hesitancy was a pan-Indian issue that currently affects the remaining polio-endemic areas.

According to Arora, in 2017–2018, a wide-age immunization campaign for measles and rubella was conducted in India, with almost 450 million children under the age of 15 being immunized. Initially, in South India a belief that the measles, mumps, and rubella (MMR) vaccine caused autism affected uptake. While the vaccination coverage rate in South India had been at 90–95 percent, it fell to around 30 percent. Special communications strategies helped rates recover in this region. However, around the same time, similar vaccine hesitancy and refusal issues emerged in a wide-age MMR immunization campaign in Indonesia. Within 4–6 months, an additional challenge emerged when a religious group began asking for a government

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¹¹ More information about Biological E is available at https://www.biologicale.com (accessed November 5, 2020).

certification that vaccines are halal. Arora said that in the past 2–3 years, the vaccination program in Indonesia has been waxing and waning. A recent evaluation of Indonesia’s National Immunization Technical Advisory Group immunization program and another vaccine program indicated that the downward trend persists.

A mechanism has developed in some communities requiring vaccines to undergo religious screening and approval, noted Arora.¹² In trying to address misinformation from anti-vaccine groups, the root cause of its spread has been considered, and the scientific logic and reasons for it have been explored. However, Arora emphasized, a time may come in the near future in which communication alone is no longer effective in meeting this challenge, and a different kind of strategy is needed. He suggested that when vaccines have to undergo a filter other than national regulatory authorities—such as by requiring some sort of religious screening or approval—new strategies to address this challenge will be needed to prevent the spread of vaccine refusal.

Innovative Approaches to Improving Vaccine Uptake

Presented by Monika Naus, British Columbia Centre for Disease Control

Naus addressed current trends in British Columbia. Canada has a publicly funded national immunization program that is managed, along with health care services, at the provincial and territorial level. She perceives Canada to have an east-to-west gradient in terms of vaccine acceptance, with the highest levels of vaccine uptake in the Maritimes region in the eastern part of the country. British Columbia is in the west and has approximately 5.1 million inhabitants. It uses a mixed delivery model in which both physicians and public health practitioners, and increasingly pharmacists as well, are responsible for immunization services. In contrast, immunizations are delivered exclusively via public health in the Maritimes, and especially in Newfoundland where vaccine uptake is highest.

Naus said that as new immunizers enter the immunization service delivery arena, some moral panic has occurred among public health practitioners, who may have different models of care delivery. A growing number of vaccines requires confidence to be maintained in older vaccines and simultaneously established during the introduction of new vaccines developed through novel technologies. New vaccines may have target populations that are less familiar, such as pregnant women. It is increasingly recognized that not all vaccines are perceived the same way. For instance, the challenges in promoting the use of

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¹² Arora highlighted the parallels of this with the experience of the Somali American communities in Minnesota that was discussed by Dr. Stinchfield earlier.

human papillomavirus vaccines are different than those used with bacterial meningitis vaccines. Gaps in primary care must also be addressed, she said.

In British Columbia, approximately 20 percent of residents are unattached to a family doctor, with the use of walk-in clinics increasing. This reduces the ability to have a relationship with a trusted health care provider, which Naus added has been repeatedly identified at this workshop as the most important driver of vaccine acceptance. She said research is needed to determine whether it is possible to establish that level of trust quickly with a provider one is seeing for the first time at any given visit. Efficiencies also need to be developed, as immunization is a public health program that ultimately must be delivered on a one-on-one basis; it is not possible to mass distribute vaccines such as by putting it in the water supply.

Naus highlighted some innovative efforts that have been made in Canada in recent years. Paul Bramadat, professor of religious studies at the University of Victoria, Canada, collaborated with a number of contributors from anthropology, history, psychology, behavioral science, law, family medicine, pediatrics, epidemiology, regulation, and public health to create the volume Public Health in the Age of Anxiety: Religious and Cultural Roots of Vaccine Hesitancy in Canada (Bramadat et al., 2017). Naus said the religious and cultural aspects of vaccine hesitancy are an increasingly important area of focus, and this book outlines the broader context, varied perspectives, and larger societal influences that have led to the current crisis of trust and truth, relativism in expertise, and regulatory acquiescence to public demand for homeopathy.

Other efforts include ImmunizeBC posting personal accounts of death and illness caused by infection from vaccine-preventable disease.¹³ These include a video about Leo Chan, a young man who died of serogroup Y meningococcal disease at age 19. The clip features a photo taken of Leo Chan with Canadian Prime Minister Justin Trudeau. Naus described that public health is beginning to embrace the power of the narrative to engage human emotions, to “speak to the elephant in our brains and not just the rider.”¹⁴ She acknowledged this can be uncomfortable for scientists who have been trained to speak about evidence and avoid anecdotal information.

A third edition of an immunization communication tool has been released in British Columbia and has been deployed in other jurisdictions.¹⁵

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¹³ More information about ImmunizeBC is available at https://immunizebc.ca/stories (accessed November 5, 2020).

¹⁴ This concept is from Jonathan Haidt’s book The Happiness Hypothesis: Finding Modern Truths in Ancient Wisdom (2006).

¹⁵ More information about ImmunizeBC’s Immunization Communication Tool for Immunizers is available at http://www.bccdc.ca/resource-gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Immunization/Vaccine%20Safety/BCCDCICT_300315.pdf (accessed November 5, 2020).

It assists immunizers in having difficult conversations with parents in terms of how to approach these discussions and provides information for answering myriad questions. Naus noted that the third addition introduces motivational interviewing as a potentially successful way to have these conversations. Lastly, evidence-based tools for addressing the pain associated with immunization are being used.¹⁶ These are focused on children and improve the experience of pain and reduce anxieties and needle phobias.

The goal of all public health immunization programs is to achieve and maintain high levels of vaccine uptake; thus, the slowness of growth or stagnation of coverage rates has been demoralizing for public health, Naus described. While the Canadian national coverage goals for almost all vaccines are around 95 percent, almost no jurisdiction has achieved these rates, and in British Columbia the 2018 coverage rate for children up to date on vaccines by their second birthday was 74.3 percent.¹⁷ Naus noted that despite the vaccination rates, disease control efforts have been effective. Many of those who are unvaccinated are clustered geographically by beliefs, both religious and nonreligious. Despite a large measles outbreak in 2014 with more than 600 cases, there was no transmission outside of the community. Naus added that for all children, the percentage that are unvaccinated is about 1 percent.

Naus pointed out that immunization registries enable researchers to use geographic information system mapping and Tableau to demonstrate where vulnerable populations are located.¹⁸ In 2019, prior to the COVID-19 lockdowns and travel restrictions, several importations of measles into British Columbia occurred (BC Centre for Disease Control, 2019). One of these resulted from three unvaccinated teenage siblings who traveled to Southeast Asia and returned with measles. This resulted in a relatively small outbreak within households and two schools, causing 10 additional confirmed cases. Intense media scrutiny of measles followed the outbreak, which was concurrent with, but unrelated to, several outbreaks in the United States. This media attention and public concern led to large-scale policy changes, including a 3-month catch-up program of MMR. Additionally, a Vaccination Status Reporting Regulation involving school mandates was passed for the

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¹⁶ More information about support tools to improve students’ experience of school-based vaccines is available at http://www.bccdc.ca/resource-gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Immunization/Vaccine%20Safety/BCCDCICT_300315.pdf (accessed November 5, 2020).

¹⁷ More information about the BC Centre for Disease Control Childhood Immunization Coverage Dashboard is available at http://www.bccdc.ca/health-professionals/data-reports/childhood-immunization-coverage-dashboard (accessed November 5, 2020).

¹⁸ More information about Tableau is available at https://www.tableau.com/solutions/maps (accessed November 5, 2020).

first time in British Columbia,¹⁹ where there had previously been reluctance to introduce mandates. Naus said that the takeaway from this outbreak response is that opportunities to move the agenda ahead should be taken advantage of when they present themselves.

Naus also highlighted a platform called Kids Boost Immunity that has been launched in many schools throughout Canada.²⁰ Using a gaming platform, it engages the next generation, Gen Z, with online education that addresses health literacy regarding vaccines, several aspects of school curriculum, and critical thinking skills including critically appraising misinformation, Naus detailed. Children are motivated through a gaming platform with leaderboards to track student learning outcomes and encourage friendly competitions. Pilot evaluations have indicated improved knowledge and increased support for immunization among students, while also meeting the needs of teachers. Now supported by the Public Health Agency of Canada, other countries are showing interest in the platform, she added.

Referencing a print by the British caricaturist James Gillray of a crowd developing bovine traits after cowpox vaccine, Naus remarked that vaccine misinformation and panic about vaccines have been around for a very long time. She said playing the “long game” is needed, and cited a prediction from Paul Bramadat, director of the Centre for Studies in Religion and Society at the University of Victoria, Canada, that moral panic will fade away. COVID-19 vaccines provide the opportunity to move ahead on these issues, she suggested. For example, mask wearing during the pandemic suggests that the public is more ready to accept new ideas than might be assumed. Additionally, the “silent majority” of people, including children and young people, are supportive of immunization, and they need safe ways to have immunization conversations. Furthermore, the needs at the population level, group level, and at the individual level must be met, engaging immunizers of all types through innovative approaches while continuing to build infrastructure, including immunization registries, information systems, and efficiencies. Naus noted her appreciation of the ability that web interfaces like Zoom provide in spreading information via forums, which enables the sharing of information and successful strategies and avoiding reinventing the wheel. Lastly, Naus noted the similarities of vaccine hesitancy issues across the globe and the potentially wide applicability of these tools and strategies, mentioning that vaccine hesitancy often stems from affirmation

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¹⁹ More information on Vaccine Status Reporting Regulation in British Columbia is available at https://www.bclaws.gov.bc.ca/civix/document/id/complete/statreg/146_2019 (accessed December 18, 2020)

²⁰ More information about Kids Boost Immunity is available at https://www.kidsboostimmunity.com (accessed November 5, 2020).

of the wonders of the body, of nonviolence, and of universal harmony and peace; some of the issues related to vaccine hesitancy are coming from a good place.

Community Polio Vaccination Efforts in Pakistan

Presented by Jean-Marc Olivé, Independent Consultant

Olivé spoke of his work supporting immunization in Pakistan in the past 8 years, specifically in efforts to increase acceptance of oral polio vaccine in the most resilient reservoir. He noted that Pakistan and Afghanistan are the last two global reservoirs of wild polio virus. In Pakistan, challenges to vaccine coverage include both access and demand issues. Approximately 61 percent of the nation’s population live in rural areas, and less than 50 percent of people in Pakistan have access to basic services. While the national diphtheria, tetanus, and pertussis (DPT) vaccine coverage rate is at 75 percent, regional rates vary greatly, ranging from 89 percent to 37 percent, depending on the province. Similar disparities exist between different ethnic groups. This is particularly true in Karachi, one of the most resilient polio reservoirs. A 2014 study conducted by the Aga Khan University indicated the overall DPT dose 3 coverage rate in Karachi was around 75 percent, the same as the national coverage level (Siddiqui et al., 2014). However, variance was seen in ethnic groups. Whereas 82 percent of the Punjabi speaking population was immunized, these rates fell to 67 percent for Pashtun speakers and 48 percent for the Bengali-speaking population.

The Pashtun-speaking population accounts for one-third of the 14,000 non-polio acute flaccid paralysis cases reported annually and two-thirds of the wild polio virus cases, Olivé reported. He described the Pashtun-speaking population as very traditional, relatively closed, and difficult to reach due to constant movement between Pakistan and Afghanistan. He added that it can be challenging for outsiders to develop trust with this community. Repeated national and subnational immunization days are organized, often on a monthly basis, with coverage averaging 95 percent. Yet, these efforts have not been able to compensate for the poor level of basic routine protection, and wild polio virus transmission has thus never been interrupted.

Efforts were initiated to map and refer children identified as previously having received a vaccination during an oral polio vaccine campaign. However, Olivé said it was soon realized that the essential immunization services did not have the capacity to access and vaccinate these children, as they could offer doses of routine vaccination to only 30 percent of them. In response, polio eradication was integrated into the national essential immunization program, and it was provided with additional funding, making the program more financially sustainable. With increased intensity of the vaccination

campaign, stronger refusal and resentment against polio vaccine emerged, Olivé described. In response to repeated visits from campaign workers, community households complained that workers were always knocking on their doors offering only polio drops and ignoring all their other problems. Lacking access to water, sanitation, school, and basic services, some community members resented that vaccines were the only service being offered.

Olivé said that in order to enhance acceptance of vaccination offered through campaigns of essential immunization services, specific communities must be listened to and given attention. He stated that to build the confidence in the community, proper health services must first be established. Steps to address needs beyond vaccination were taken in a higher-risk community, including opening a new, revamped facility, approaching human resource issues as a lack of accountability, and addressing shortages of female health workers and staff able to speak Pashtun. This was done with the participation of local nongovernmental organizations. Olivé said that with the revamped, newly created health facility, an integrated service flow was established, directing children from birth registration to Expanded Programme on Immunization screening, nutrition screening, administering necessary vaccines, nutrition counseling, providing needed food supplements, and finally reaching the outpatient clinic as a final step in getting needed medicine. Integrated outreach services were also organized to bring health services closer to the community, including vaccination, Child Health Day, referrals for nutrition problems, promotion of breastfeeding, and birth registration. Additionally, engagement with the community involved installing a filtration station and supporting waste management, he added.

Efforts in this specific community resulted in significant increases in coverage. According to Olivé, the DPT 2018 coverage rate of 17 percent more than doubled to 38 percent in 2019, and inactivated polio vaccine moved from 17 to 42 percent. Because of the COVID-19 pandemic, progress has halted, yet the figures have not returned to the 2018 rates. Olivé was hopeful that the provision of integrated service will improve community conditions and, by extension, trust in the health system and positive perception toward vaccination. Ultimately, polio vaccination will enable the final eradication of wild polio virus circulating in these remaining persistent reservoirs, he concluded.

DISCUSSION

Addressing Vaccine Acceptance During the COVID-19 Pandemic

Given the decline in immunization services during the COVID-19 pandemic, and knowing that efforts will need to be intensified in order to bring coverage rates to pre-pandemic levels, Cohn asked the panelists

about opportunities that may emerge from the pandemic in terms of vaccine acceptance and coverage rates. Hotez replied that this is a troubling time. CDC has reported a fairly steep decline in MMR vaccination coverage in the United States owing to a previous emergency order.²¹ While the MMR coverage rate is beginning to recover, Hotez stated that he is concerned it will not return to full capacity because of the aggressive efforts of the antivaccine movement. He suggested a worst-case scenario of contending with COVID-19, influenza, and possibly measles concurrently. The opportunity lies in redoubling efforts around vaccine advocacy. Hotez called for an open and expanded vaccine advocacy campaign in the United States in which COVID-19 vaccinations should be integrated into the messaging about other types of vaccinations.

In Canada, COVID-19 has brought many “talking heads into the sphere,” said Naus. In addition to leaders at the national level and provincial health officers, family doctors, infectious disease physicians, and others are providing good information to the public via media interviews and other platforms. This is an opportunity to be more transparent and to engage a broader segment of the immunizer and health workforce in answering questions from the public. This includes professionals who actually speak with patients on the frontline far more than immunizing managers might, as public health experts often work behind the scenes in planning and policy, Naus said. Thus, she finds this development to be useful and productive. Furthermore, she emphasized the need to be more transparent with information as it becomes available to experts. While the amount of information coming out in real time can seem overwhelming, opportunities should be seized to frame this information and disseminate it in a timely fashion. She maintained that in British Columbia, repeated surveys show that vaccine safety is a key driver of decision making for parents who choose not to vaccinate—not access issues, which have largely been addressed. The likelihood that multiple COVID-19 vaccines are forthcoming could present an opportunity for researchers to share how they arrive at information about vaccine safety.

Arora noted that the COVID-19 pandemic caused substantial disruption to the health system in general and vaccine coverage decreased as immunization services were halted. However, in India, immunization services have been used as an entry point to reengineer and rebuild the health system. Vaccine acceptance has been high, particularly in the context of community expectations for an upcoming COVID-19 vaccine. To address the challenge of meeting the public’s expectations for the efficacy and safety of COVID-19 vaccines, he suggested that the scientific and public health communities should develop a transparent and proactive communication strategy.

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²¹ See https://www.cdc.gov/mmwr/volumes/69/wr/mm6919e2.htm (accessed May 24, 2021).

Olivé said the pandemic has brought an opportunity to raise vaccine coverage rates in general. In polio-endemic countries, the polio infrastructure has been used to control the COVID-19 outbreak via surveillance, contact tracing, and delivering messages to the population regarding distancing, safety measures, and handwashing. All of this has been done by polio and health center staff. In going house to house, communities have come to realize that vaccinators have something to offer other than vaccine drops. Thus, Olivé was optimistic this will strengthen the acceptance of vaccination in the community. He noted that during recent national immunization days in Pakistan, the uptake of the polio vaccine seemed to have increased to levels it had achieved in the past.

Transparency and Data Communication

In the context of misinformation, Cohn asked how vaccine safety monitoring and data can be communicated to the public in a transparent way that introduces confidence. Arora responded that in India, the national Adverse Events Following Immunization (AEFI) committee was secretive and did not share causality assessment findings, which encouraged the anti-vaccine lobby and led to negative press coverage of vaccines. When he chaired the national AEFI committee, all causality assessment data were made publicly available—including cases of serious and severe adverse events and their causality—which deflated the anti-vaccine lobby because the press stopped covering the topic. Arora noted this type of transparency was particularly relevant in relation to the pentavalent vaccine. The anti-vaccine lobby was attributing sudden infant deaths to the pentavalent vaccine, but transparency via providing data prevented the lobby from gaining traction.

Discussions around COVID-19 vaccines have revealed that the American public does not realize how robust the vaccine safety monitoring system is, said Hotez. The public in the United States does not understand what CDC and FDA do, how they conduct phase 3 trials, what the Vaccines and Related Biological Products Advisory Committee and WHO’s Advisory Committee on Immunization Practices are, or the monitoring conducted after a vaccine is released via VAERS, the Vaccine Safety Datalink, and at least two other systems, Hotez contended. While the vaccine safety monitoring systems in the United States are some of the most robust the world has ever seen, the American public is hearing about them for the first time, underscoring the need to build awareness. Olivé added that in developing countries, all adverse events related to immunization should be communicated by the government. Experts should share both what is known and what is not known; the media should also receive education so they can report these stories more constructively.

Building Trust Around Vaccination

Noting the time-intensive nature of gaining religious approval and establishing trust with patients, Cohn asked about the feasibility of approaching each of the vast number of religious leaders to gain their approval for their constituents to receive vaccines. Furthermore, as health care providers have increasingly limited time with their patients, Cohn asked about ways to institutionalize trust. The patient–provider interaction is critical in maintaining trust, but she asked whether trust can be built with communities and individuals outside of systems that use a one-by-one approach. Arora replied that the issue of institutional versus individual trust cannot be addressed by technical or communication experts alone—it also requires bureaucratic and political leadership. These efforts should span the institutional and community levels in addition to the individual and household levels, he asserted.

Hotez remarked that the bandwidth of anti-vaccine groups is increasing on the Internet and on social media. Thus, when parents try to find information on the Internet, they are often inundated with misinformation. Experts engage in much discussion about how to refine and improve messaging, but increasingly this message seems to be “a message in a bottle in the Atlantic Ocean,” he said. As misinformation continues to become more dominant, a more proactive approach to removing it is warranted. Arora added that a single statement in the United States associating vaccine with autism can cause much damage, so misinformation needs to be tackled at various levels to make an impact.

Cohn closed the discussion by asking each participant to provide one word that participants should take from these sessions to integrate into the way they approach increasing vaccine confidence in the communities where they live and work. Naus replied, “multidisciplinary collaboration.” Hotez contributed, “track record,” noting the incredible global and U.S. national track record of success in vaccine safety. Arora said, “honest and proactive.” Olivé offered, “build trust.”

CLOSING REMARKS

Daszak said that the issue of vaccine hesitancy is at the core of the complexity of the issues faced by global health and national public health. Health and choices around health are deeply personal issues for everyone. However, in the context of vaccination, those individual choices affect everyone—more so than any other health choice—which is the dilemma at hand. He highlighted the role of building trust with people who do not agree about this issue and with people who have been given misinformation by willful organizations in a nefarious way, persuading them not to take vaccines when it is for their benefit. The workshop spotlighted examples of solutions to

building trust in those communities, including activism and governmental information and communication. Everything points to openness, honesty, and transparency in how professionals communicate, Daszak noted, and to do these things frequently. When misinformation is presented it should be approached and confronted, sometimes via forceful correction and sometimes sensitively. The COVID-19 pandemic has taught the world that each individual’s actions and choices directly affect other people in their homes, neighborhoods, communities, and beyond. Vaccine hesitancy is part of that lesson. Daszak was optimistic that once COVID-19 vaccines are available and government campaigns to promote uptake of these vaccines are under way, a future will emerge in which the public is better informed and everybody understands how individual actions affect everyone.