Contributions of the model of rhesus macaque infection by sivmac to the understanding of the pathophysiology of human infection by HIV and to the development of a vaccine

Experimental infection of macaques with sivmac constitutes the best animal model of human HIV infection. Indeed, HIV is genetically related to HIV, it presents the same cellular tropism and induces in a few months a pathology similar to AIDS. This model therefore constitutes a good tool to better understand the pathophysiology of HIV infection, and the testing of vaccine preparations we examined immune parameters and viral load during the early stages following infection by the pathogenic virus. sivmac251 and the sivmac251deltanef virus attenuated by deletion of the nef gene. In the context of an infection by the pathogenic virus, we have shown: (1) the initial viral load is little dependent on the inoculum dose; (2) infection is followed by a peak of ifn-a production which precedes but is not capable of limiting the initial replication peak; (3) the production of most cytokines is stimulated after infection and we have not been able to highlight any particular profile associated with the effectiveness of the control of viral replication; however (4) an association could be established between the level of ifn-g and the level of circulating p27 antigenemia, suggesting a beneficial effect of ifn-g; (5) the effectiveness of the reduction of the initial viral load is a predictive factor of subsequent evolution. From a vaccination perspective, we also infected monkeys with the attenuated sivmac251deltanef virus, a portion of which was then subjected to a challenge inoculation with the pathogenic sivmac251 virus. To date, the only truly effective vaccine preparation is based on the use of a live virus attenuated by inactivation of the nef gene. We have shown in these animals that: (1) infection with the attenuated virus induces a much lower viral load than the pathogenic virus in naive animals; (2) the animals did not develop any pathology after five years of observation; (3) vaccinated animals are not fully protected against infection by the potentially pathogenic challenge virus, although these animals did not develop pathology five years after challenge inoculation.