The Ebola Epidemic in West Africa Proceedings of a Workshop (2016) / Chapter Skim
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Appendix B: Ebola: A View from the National Institute of Allergy and Infectious Diseases
Appendix B: Ebola: A View from the National Institute of Allergy and Infectious Diseases
Pages 73-86
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From page 73... ...
has been engaged with a full spectrum of research activities on Ebola virus and other related filoviruses predating this outbreak by several decades. Activities have included basic virology, the development of Ebola-specific vaccines, therapeutics, and diagnostic tests, culminating in multiple candidate products undergoing clinical evaluation for the first time during an ongoing Ebola virus outbreak.
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From page 74... ...
Since previous Ebola outbreaks were successfully stopped with infection control procedures and contact tracing, specific medical countermeasures such as vaccines and therapeutics had not proceeded to advanced development. Throughout this outbreak and extending decades prior, NIAID has supported research with Ebola virus as well as other members of the filovirus family, including basic virology, vector identification, development of vaccines, therapeutics, diagnostics, and clinical research.
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From page 75... ...
. Ebola as a Species-Specific Infectious Agent with Immune Evasion Strategies The Ebola virus possesses specific gene products that mediate immune evasion, especially early responses by the innate immune system, which is partly responsible for the severe virulence and systemic pathology that are observed with Ebola virus infection (Audet and Kobinger, 2015; Ramanan et al., 2011)
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From page 76... ...
In the presence of both trimer GP and sGP, the antibody response skews in favor of the cross-reactive set, and the adaptive humoral immune response is compromised because sGP can function as a decoy. In the presence of only trimer GP, the cross-reactive antibody responses are reduced, while enhancing trimer GP reactivity, thus focusing the humoral response toward antibodies more likely to participate in viral clearance.
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From page 77... ...
containment. Second, the species specificity of viral pathogenesis described above, renders traditional small, rodent animal models less informative compared to other infectious agents, necessitating studies with nonhuman primates (NHPs)
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From page 78... ...
. In addition, immunoglobulin from vaccinated primates that are protected from subsequent challenge fails to mediate protection by passive transfer, but passive transfer of immunoglobulin derived following vaccination and after survival from challenge can mediate protection (Dye et al., 2012; Parren et al., 2002)
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From page 79... ...
. Given the species specificity of Ebola virus along with potential species-specific mechanisms of the drugs themselves, caution is warranted with interpretation of animal model results, as well as drawing conclusions regarding human dosing.
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From page 80... ...
PCR relies on the availability of genomic information, and the recent advances in genomic technologies offer new opportunities for outbreak assessment, including whole viral genome sequencing. During this outbreak, Ebola virus dynamics were directly observed based on sequencing viral isolates obtained during the outbreak (Gire et al., 2014; Park et al., 2015)
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From page 81... ...
And so, while evolving technology has allowed medical science to identify newly emerging infectious diseases with ever increasing speed and precision, vigilance is required to avoid surprise from a reemerging infectious disease that professional experience and textbooks assert has been addressed, whether that be a novel clinical presentation, enhanced transmission, or emerging drug resistance. The ability of the biomedical research enterprise to respond expeditiously and effectively to future outbreaks of Ebola virus as well as other emerging infectious diseases depends on comprehensive, sustained research efforts that span the full range of scientific and medical investigations from basic research through translational science to clinical research and testing prior to an outbreak, during the outbreak, and extending well after any particular outbreak has ended.
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2015. Immune evasion in Ebolavirus infections.
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2012. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.
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2002. Pre- and postexpo sure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody.
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2015. A recombinant vesicular stomatitis virus Ebola vaccine -- preliminary report.
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2012. A characterization of aerosolized Sudan virus infection in African green monkeys, cynomolgus macaques, and rhesus macaques.
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