Vaccine Research and Development to Advance Pandemic and Seasonal Influenza Preparedness and Response Lessons from COVID-19 (2022) / Chapter Skim
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1 Introduction
1 Introduction
Pages 11-36
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, have both called for improving influenza vaccines with respect to both effectiveness and scalable manufacturing technologies. As demonstrated throughout the response to COVID-19, the process of R&D of novel vaccines can be significantly optimized when stakeholders are provided with the resources and technologies needed to support research and when data are shared in real time (Kinsella et al., 2020)
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The discussions of this international committee served as the basis for the statements of task for the ad hoc committees charged with conducting the four concurrent National Academies consensus studies. The present report was produced by the Committee on Vaccine Research and Development Recommendations for Advancing Pandemic and Seasonal Influenza Preparedness and Response, convened to identify opportunities for optimizing vaccine R&D processes in the event of an influenza pandemic, and to determine whether those opportunities could be used to inform the development of seasonal and universal influenza vaccines.
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6. Recommend ways to build capacity for accelerated vaccine development and delivery against pandemic influenza viruses, and discuss the applicabil ity of rapid-response procedures for seasonal influenza outbreaks.
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Figure 1-1 shows how each major element of the Statement of Task maps to the chapters of the report. The content of this report was informed by the extensive expertise of the committee members, which was applied in formulating recommendations for improving influenza vaccine R&D.
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FIGURE 1-1 Mapping the major elements of the committee's Statement of Task to the chapters of this report. NOTES: The committee will address seven major themes, outlined above in their corresponding chapters.
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This section provides brief background information on the following: • influenza virus and its effects on humans, • viral antigenic drift and shift and the implications for influenza vaccine development, • the landscape of influenza vaccine platforms, • the effectiveness of seasonal influenza vaccines, • the potential for developing a universal vaccine, and • vaccine development in the context of the COVID-19 pandemic. Chapter 2 delves into several of these topics in greater detail.
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SOURCE: LePan, 2021. Disease Caused by Influenza Viruses The influenza virus HA attaches to the terminal α-sialic acid on the surface of the host cell and this strong binding initiates the endocytosis process (Luo, 2012)
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Alveolar macrophages play an important role in the innate immune response and limit the spread of the virus by phagocytosis of infected cells. Dendritic cells present antigen to CD4+ and CD8+ T cells to stimulate adaptive cellular responses and can exert cytolysis (interferon killer dendritic cells)
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. Viral Antigenic Drift and Shift and Implications for Vaccine Development Influenza viruses are characterized by their ability to rapidly undergo antigenic changes caused by mutations in the antibody-binding sites of the HA and NA viral surface proteins, a process called antigenic drift.
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The Landscape of Influenza Vaccine Platforms Egg-Based Vaccine Platform About 95 percent of the licensed seasonal influenza vaccines are manufactured in embryonated chicken eggs. The trivalent inactivated vaccine (TIV)
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However, egg allergy is not a contraindication to receiving influenza vaccine in many countries (Pushko and Tretyakova, 2020)
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Therefore, this method requires extensive screening, and the process might have to be intensified to obtain the required yield. Recombinant Influenza Vaccines Another seasonal influenza vaccine platform that does not use chicken eggs is the recombinant protein influenza vaccine system.
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. Effectiveness of Seasonal Influenza Vaccines Vaccine effectiveness (VE)
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. HI antibody titers are widely used and are accepted by regulators as a correlate of protection for inactivated influenza vaccines, given that this surrogate is reasonably likely to provide clinical benefit.
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Universal Vaccine Development Given the antigenic drift of influenza viruses and limitations with regard to long-lasting antibody response, there is a need to provide seasonal vaccines every year. Targeting the more conserved regions of the virus and improving vaccine-induced immunity could potentially mitigate these issues.
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Infected cells produce high levels of these proteins and present the antigens on major histocompatibility complex molecules, which may elicit cellular immune responses. Therefore, these proteins are investigated as potential targets for T cell-based vaccines (Carragher et al., 2008)
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However, whether these platforms indeed improve the immunogenicity for influenza vaccines remains to be investigated. Vaccine Development in the Context of the COVID-19 Pandemic After the WHO Country Office in China was notified of cases of pneumonia with unknown cause in Wuhan, China, on December 31, 2019 (WHO, 2020a)
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Journal of Infectious Diseases 206(8)
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2011. A fast track influenza virus vaccine produced in insect cells.
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2020. Preexisting immunity shapes distinct antibody landscapes after influenza virus infection and vaccination in humans.
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2015. Cell culture-based influenza vaccines: A necessary and indispensable investment for the future.
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2015. Current and emerging cell culture manufacturing technologies for influenza vaccines.
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2018. Re port on eighth WHO meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses: Chicago, USA, 23–24 August 2016.
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2018. Adjuvanted influenza vaccines.
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2013. Traditional and new influenza vaccines.
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