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Can a T-Cell Vaccine Block Escape?

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War in the Body

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Abstract

Since Edward Jenner’s 1796 experiment, now unacceptable to institutional review boards (he inoculated a boy with pus from a cowpox-infected milkmaid’s scab, then with smallpox), scientists have tested a plethora of vaccine concepts. Louis Pasteur discovered, somewhat by accident, the first “live-attenuated” vaccine (it was an aging culture of fowl cholera), a weakened preparation of the disease agent that still replicates in the host and generates immunity.

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Notes

  1. 1.

    Zagury later injected his vaccine into 18 children in Zaire, with permission from Zairean, but not European, officials, and was criticised on ethical grounds.

  2. 2.

    The phases of clinical research are labeled I–III; phase I trials are small and address biological response and safety concerns; phase II are larger, often in the range 1K–3K and generate data about biological action and limited information about efficacy; phase III are large licensure trials, with numbers depending on the “attack rate” of the disease.

  3. 3.

    An author of this book (W.D.W.) entered the HIV field when HIVNET was founded.

  4. 4.

    “The focus on drugs and vaccines made sense a decade ago, but it is time to acknowledge our best hunches have not paid off…we need to put increased emphasis on basic science…” Field’s comments reflected the eternal tension between mechanists and empiricists. Several years later, his colleagues Bruce Weninger and Max Essex, prompted by NIH’s creation of AVRC headed by David Baltimore (a Nobelist in biology and medicine but not a vaccinologist) replied, again in Nature: “the theorists leisurely pursue new knowledge to build models to explain and perhaps offer elegant solutions. The empiricists apply existing knowledge to seek pragmatic answers…”

  5. 5.

    Francis was furious about the June 17th decision, saying understandably, if hyperbolically, “They had no idea that what they did was kill vaccines.”

  6. 6.

    Statisticians warn against such post hoc subgroup analyses, because the trial was not designed with sufficient power to estimate effects in smaller groups.

  7. 7.

    W.D.W. thanks Fusheng Li of the FHCRC for relating these ideas.

  8. 8.

    If the “primary viremia drives the epidemic” theory is true, such a vaccine might provide a benefit, but it would certainly be hard to convince the FDA to license it based on data resembling Figure 12.2.

Bibliography

  1. Amara RR, Villinger F, Altman JD, Lydy SL, O’Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL (2001) Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292(5514):69–74

    Article  PubMed  CAS  Google Scholar 

  2. Barouch DH et al (2003) Viral escape from dominant simian immunodeficiency virus epitope-specific cytotoxic T-lymphocytes in DNA-vaccinated Rhesus monkeys. J Virol 77:7367–7375

    Article  PubMed  CAS  Google Scholar 

  3. Blume S, Geesink I (2000) A brief history of polio vaccines. Science 288(5471):1593–1594

    Article  PubMed  CAS  Google Scholar 

  4. Duerr A, Wasserheit JN, Corey L (2006) HIV vaccines: new frontiers in vaccine development. Clin Infect Dis 43(4):500–511

    Article  PubMed  CAS  Google Scholar 

  5. Frahm N, Kiepiela P, Adams S, Linde CH, Hewitt HS, Sango K, Feeney ME, Addo MM, Lichterfeld M, Lahaie MP, Pae E, Wurcel AG, Roach T, St John MA, Altfeld M, Marincola FM, Moore C, Mallal S, Carrington M, Heckerman D, Allen TM, Mullins JI, Korber BT, Goulder PJ, Walker BD, Brander C (2006) Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat Immunol 7(2):173–178

    Article  PubMed  CAS  Google Scholar 

  6. Goulder PJ, Watkins DI (2004) HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol 4(8):630–640

    Article  PubMed  CAS  Google Scholar 

  7. Haigwood NL (2004) Predictive value of primate models for AIDS. AIDS Rev 6(4):187–198

    PubMed  Google Scholar 

  8. Hu SL (2005) Non-human primate models for AIDS vaccine research. Curr Drug Targets Infect Disord 5(2):193–201

    Article  PubMed  CAS  Google Scholar 

  9. Johnston M, Fauci AS (2007) An HIV vaccine—evolving concepts. New Engl Rev Med 356:2073

    Article  CAS  Google Scholar 

  10. Kaul R, Rutherford J, Rowland-Jones SL, Kimani J, Onyango JI et al (2004) HIV-1 Env-specific cytotoxic T-lymphocyte responses in exposed, uninfected Kenyan sex workers: a prospective analysis. AIDS 18:2087–2089

    Article  PubMed  Google Scholar 

  11. Klenerman P, Zinkernagel RM (1998) Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. Nature 394:482–485

    Article  PubMed  CAS  Google Scholar 

  12. Li F, Horton H, Gilbert PB, McElrath JM, Corey L, Self SG (2007) HIV-1 CTL-based vaccine immunogen selection: antigen diversity and cellular response features. Curr HIV Res 5(1):97–107

    Article  PubMed  CAS  Google Scholar 

  13. Li F, Shao Y, Wick WD, Beyrer C, Gilbert P, McElrath J, Corey L, Self S (2008) Enhancing the epitope coverage of HIV-1 T-cell vaccines. Preprint

    Google Scholar 

  14. Liu J, Ewald BA, Lynch DM, Nanda A, Sumida SM, Barouch DH (2006) Modulation of DNA vaccine-elicited CD8+ T-lymphocyte epitope immunodominance hierarchies. J Virol 80(24):11991–11997

    Article  PubMed  CAS  Google Scholar 

  15. Mascola JR, Snyder SW, Weislow OS, Belay SM, Belshe RB, Schwartz DH, Clements ML, Dolin R, Graham BS, Gorse GJ, Keefer MC, McElrath MJ, Walker MC, Wagner KF, McNeil JG, McCutchan FE, Burke DS (1996) Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. J Infect Dis 173(2):340–348

    CAS  Google Scholar 

  16. McDermott AB, O’Connor DH, Fuenger S, Piaskowski S, Martin S, Loffredo J, Reynolds M, Reed J, Furlott J, Jacoby T, Riek C, Dodds E, Krebs K, Davies ME, Schleif WA, Casimiro DR, Shiver JW, Watkins DI (2005) Cytotoxic T-lymphocyte escape does not always explain the transient control of simian immunodeficiency virus SIVmac239 viremia in adenovirus-boosted and DNA-primed Mamu-A*01-positive rhesus macaques. J Virol 79(24):15556–15566

    Article  PubMed  CAS  Google Scholar 

  17. McMichael AJ, Hanke T (2003) HIV vaccines 1983–2003. Nat Med 9:874–880

    Article  PubMed  CAS  Google Scholar 

  18. Moore JP, Cao Y, Qing L, Sattentau QJ, Pyati J, Koduri R, Robinson J, Barbas CF 3rd, Burton DR, Ho DD (1995) Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120. J Virol 69(1):101–109

    PubMed  CAS  Google Scholar 

  19. Staprans SI, Feinberg MB (2004) The roles of nonhuman primates in the preclinical evaluation of candidate AIDS vaccines. Expert Rev Vaccines 3(4 Suppl):S5–S32

    Article  PubMed  Google Scholar 

  20. The Scientist, 1 April 1996, 10:14

    Google Scholar 

  21. Thomas P (2001) Big shot: passion, politics, and the struggle for an aids vaccine. Public Affairs, NY

    Google Scholar 

  22. Uberla K (2005) Efficacy of AIDS vaccine strategies in nonhuman primates. Med Microbiol Immunol 194(4):201–206

    Article  PubMed  Google Scholar 

  23. Vogel TU, Reynolds MR, Fuller DH, Vielhuber K, Shipley T, Fuller JT, Kunstman KJ, Sutter G, Marthas ML, Erfle V, Wolinsky SM, Wang C, Allison DB, Rud EW, Wilson N, Montefiori D, Altman JD, Watkins DI (2003) Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239. J Virol 77(24):13348–13360

    Article  PubMed  CAS  Google Scholar 

  24. Wilson NA, Reed J, Napoe GS, Piaskowski S, Szymanski A, Furlott J, Gonzalez EJ, Yant LJ, Maness NJ, May GE, Soma T, Reynolds MR, Rakasz E, Rudersdorf R, McDermott AB, O’Connor DH, Friedrich TC, Allison DB, Patki A, Picker LJ, Burton DR, Lin J, Huang L, Patel D, Heindecker G, Fan J, Citron M, Horton M, Wang F, Liang X, Shiver JW, Casimiro DR, Watkins DI (2006) Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239. J Virol 80(12):5875–5885

    Article  PubMed  CAS  Google Scholar 

  25. Yang OO (2003) Will we be able to ‘spot’ an effective HIV-1 vaccine? Trends Immunol 24:67–72

    Article  PubMed  Google Scholar 

  26. Yang OO (2004) CTL ontogeny and viral escape: implications for HIV-1 vaccine design. Trends Immunol 25(3):138–42

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Seattle, Washington, USA

    W. David Wick

  2. Geffen School of Medicine, Department of Medicine, UCLA Medical Center, Los Angeles, California, USA

    Otto O. Yang

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Wick, W.D., Yang, O.O. (2013). Can a T-Cell Vaccine Block Escape?. In: War in the Body. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7294-0_12

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