Chapter 44 : Meeting the Challenge of Vaccine Design To Control HIV and Other Difficult Viruses

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Viruses that have evolved to frequently establish persistent infection are rarely successful targets for vaccine prevention. The clearest evidence that a virus is capable of significant immune evasion is whether or not the host can be reinfected. This review discusses the immunobiology of human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), and respiratory syncytial virus, which have evaded vaccine development. The chapter also talks about potential solutions for the elusive viral pathogens. Infection is self-limited in some individuals, suggesting that immunity is sometimes effective. Features that distinguish successful immune responses from failed responses to HCV have not yet been identified, thus complicating vaccine development. HIV-1 and HCV display extreme genetic diversity, more than any other known viral pathogen. Prior to discovery of the highly mutable RNA viruses in the 1980s, influenza had been the prototype of a viral vaccine target with genetic variation occurring through both point mutations and reassortment of genes. For HIV and HCV viruses, defining the breadth of response, the number of epitope responses needed for each incoming virus, and the extent of cross-reactive responses needed to defend against the diversity of potential infecting stains are important for the next generation of T-cell-based vaccines. The focus on early infection events should include intensive characterization of viruses that make it through the bottleneck described for transmission. This could significantly simplify the complexity of the antigenic content currently thought to be required for a preventive vaccine.

Citation: Graham B, Walker C. 2011. Meeting the Challenge of Vaccine Design To Control HIV and Other Difficult Viruses, p 559-570. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch44
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Immune strategies for coping with genetic diversity. The immune system is designed to accommodate genetic diversity among individuals and genetic diversity of microbes. T-cell epitopes are relatively conserved across viral subtypes compared to antibody epitopes. The implication is that vaccine-induced T-cell mechanisms may be of particular value for highly diverse viruses. Conversely, antibody-mediated protection against a specific structure may be achievable across diverse population groups.

Citation: Graham B, Walker C. 2011. Meeting the Challenge of Vaccine Design To Control HIV and Other Difficult Viruses, p 559-570. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch44
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Evolution of viral vaccines. The 15 available antiviral vaccines have taken over 200 years to develop. Most of the rapid advances have followed the emergence of new technologies that made vaccine development possible. Vaccines developed because of the discovery of cell culture and the ability to propagate viruses in vitro are noted in green. Vaccines developed as a consequence of tools made available by molecular biology are noted in red. Rapid advances in fields ranging from genetics to computational biology may open new possibilities for developing vaccines against difficult and emerging viral pathogens. The list of future technologies is to suggest areas in which technical advances may provide an impetus for development.

Citation: Graham B, Walker C. 2011. Meeting the Challenge of Vaccine Design To Control HIV and Other Difficult Viruses, p 559-570. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch44
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Characteristics of difficult viruses and those with successful preventive vaccines

Citation: Graham B, Walker C. 2011. Meeting the Challenge of Vaccine Design To Control HIV and Other Difficult Viruses, p 559-570. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch44
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Biological challenges for HIV vaccine development

Citation: Graham B, Walker C. 2011. Meeting the Challenge of Vaccine Design To Control HIV and Other Difficult Viruses, p 559-570. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch44

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