AIDS: Vaccine Development
Sheppard NC., Sattentau QJ.
© 2008 2008 Elsevier Ltd. All rights reserved. The best hope for curbing the HIV-1 pandemic lies in the development of a prophylactic vaccine, a challenge that has eluded vaccinologists since the discovery of HIV-1 in 1983. HIV-1 is genetically highly diverse both within infected individuals and globally. Strains vary substantially, especially in the envelope glycoproteins (Env), the only targets for virus-neutralizing antibodies. Antigenic variation, combined with multiple other immune evasion strategies, enable the virus to evade neutralizing antibodies in naturally infected hosts or in recipients of the vaccine candidates tested thus far. In vivo control of viremia appears to rely on CD8 cytotoxic T-lymphocyte (CTL) responses and such responses are frequently, but not universally, detected in highly exposed seronegative persons. Novel vaccine strategies that induce CTL responses in macaque models challenged with simian immunodeficiency virus (SIV) or SIV recombinant for HIV-1 Env (termed simian-human immunodeficiency virus) do not prevent infection but allow the control of viremia and prevention of disease progression. Conversely, infusion of broadly neutralizing monoclonal antibodies does prevent infection in macaques. An ideal vaccine strategy would probably induce both robust CTL responses and broadly neutralizing antibodies.