[8] Immunological basis for HIV vaccine development

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] IMMUNOLOGICAL BASIS FOR HIV VACCINE DEVELOPMENT

[AUTHOR(S):] Jorge Flores
Vaccine Clinical Research Branch, Division of AIDS, NIAID, National Institutes of Health, Bethesda, Maryland, U.S.A.

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 8

[ABSTRACT:] The rational development of an HIV vaccine has been complicated by the inherent risks of employing strategies that have been successful for other infections, namely viral attenuation and inactivation. Furthermore, the integration of retroviral DNA into the cell chromosome leads to a state of viral latency that resists immunological clearance, and it is possible that while vaccines may be developed that substantially ameliorate progression and impede transmission to others, they may not allow for full clearance of HIV once infection occurs.

Live virus vaccines for other viral pathogens and resolved natural infection induce a state of local and systemic immunity through a balanced specific activation and memory induction in the various arms of the immune system, i.e., B cells, and helper (CD4+) and cytotoxic (CD8+) T cells. Multiple strategies have been employed to recreate those three functions through different HIV vaccine designs and combinations. Understanding and achieving T cell immunity has progressively improved through the use of strategies based on DNA, live viral vectors, peptides and the concomitant administration of these antigens with cytokines. On the other hand, it has been thus far impossible to induce broadly neutralizing antibodies (the most desirable B cell response) with these strategies or with envelope-based subunit vaccines. Current efforts to further understand the structure/function of the viral envelope are providing important clues towards that goal, and it might be possible to successfully create the needed antigens. However, once such vaccines are developed, one major obstacle remains: how to maintain adequate levels of neutralizing antibody to provide sterilizing immunity, or accelerate B and T cell anamnestic memory responses to attain total viral clearance.

While non-human primate models have been successfully employed in evaluating vaccine candidates, understanding correlates of protection and streamlining the number of candidates entering clinical trials, the evaluation of vaccine efficacy will ultimately require large clinical trials in which immunological and virological correlates of immunity are examined at the same time that protection from infection or amelioration of disease are assessed.

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