Rapporteur report
Science Track A: Biology and Pathogenesis of HIV report by Dr. Rupert Kaul
This non-abstract session aimed to generate discussion regarding the advantages and disadvantages of three major research models for the elucidation of the immune correlates of protection against HIV. These included Highly Exposed, Persistently Negative (HEPS) individuals, those with Long Term Non Progressive infection (LTNPs), and primate models.
Rupert Kaul (Canada) summarized lessons learned from a cohort of sex workers in Nairobi, Kenya who appear to resist HIV infection despite multiple exposures. Small pilot studies had linked resistance with both HIV-specific CTL and HIV-neutralizing genital IgA antibodies, and these associations have now been confirmed in larger, prospective cohort studies. The advantage of the HEPS studies was that such individuals represent "real life" resistance to HIV. However, since many immune and genetic factors have been associated with reduced susceptibility, the lesson for the future was that larger studies need to be performed, ideally in a blinded, prospective fashion. This will enable identification of the strongest protection correlates.
Ruth Ruprecht (USA) discussed primate models of protection against HIV. She emphasized that the primate model has been able to clearly demonstrate the only proven immune correlate of protection against HIV (in the form of SHIV) challenge, namely the prior passive administration of a cocktail of four neutralizing antibodies (b12, 2G12, 2F5 and 4E10). Important lessons for the future are that the primate models need to mimic the process of human infection as closely as possible, specifically through using repeated low dose mucosal challenge with an R5 virus based on an isolate from early infection, when viruses may be more easily neutralized.
Finally, Photini Kiepiela (South Africa) presented data regarding the immune correlates of HIV immune control by CTL in a large cohort of HIV-infected participants. Distinct HLA types were strongly associated with both enhanced and impaired HIV control. This may relate to the fact that different HLA alleles "direct" the host immune response against distinct regions of the virus, and that CTL directed against Gag may be much effective (immune "drivers") than those directed against Env or the accessory proteins (immune "passengers").
The comment was made (Guio Silvestre, USA) that the natural primate hosts of several HIV-like retroviruses demonstrate high viral loads and minimal HIV-specific cellular immunity, perhaps suggesting that evolution has led to the selection of virus "tolerance" rather than resistance or strong antiviral immunity. This may have important implications for the vaccine field.
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