Vaccins contre les virus de l'immunodéficience humaine

Abstract

Definite progress has been registered in the field of human immunodeficiency virus type 1 (HIV1) vaccines following the observation that live attenuated simian immunodeficiency virus (SIV) vaccines can provide remarkable protection against wild type SIV or S/HIV challenge in rhesus macaques. Studies of the immune correlates of protection have unravelled the role of the CD8+ T-cell response, both in the form of cytotoxic T cells (CTL) and through the secretion of soluble antiviral factors including β-chemokines RANTES, MIP-1α and MIP-1β. In humans, it has been found that a few persons remain HIV seronegative and PCR negative in PBMC despite frequent HIV exposure by the mucosal route. These uninfected, highly exposed individuals show polyclonal HIV-specific CTL responses together with a secretory IgA (sIgA) response in the genital tract. Therefore, the induction of sIgA at mucosal surfaces and that of systemic and, most likely, mucosal CTL could be the highmark of an efficacious HIV vaccine. Induction of cellular immune responses is being sought at this time with various live recombinant vaccines using as a vector either a poxvirus, an alphavirus or a Salmonella strain. These vaccines have been combined with lipopeptides, naked DNA vectors and/or purified gp 120/gp 140 in various prime-boost combination strategies. Recently, a totally novel vaccine approach based on the use of the non-structural Tat or Tat and Rev proteins has also been shown to induce efficient protection from challenge with pathogenic S/HIV or SIV in vaccinated macaques. There is also hope that HIV vaccines could be used in a therapeutic approach in combination with antiviral chemotherapy to help control viral loads after therapy is stopped. However, we are still far from a practical, efficacious HIV vaccine that would be cheap, efficacious, and easy to administer on a global scale.