Grant: Catalyst Grant: HIV/AIDS Vaccine Discovery Research (Can HIV Vaccine Initiative)

The development of a vaccine against HIV-1 represents the best hope of controlling the worldwide AIDS epidemics. To date, no vaccine has been shown to be clinically useful. However, in monkeys, an attenuated SIV (simian immunodeficiency virus) belonging to the same family of viruses and causing a similar disease as HIV-1, has been shown to be a very efficient vaccine against the challenging SIV. There is a general concensus that this represents the best available and the most potent vaccine against SIV. It is presumed that a similarly attenuated HIV-1 would also be very efficient as a vaccine. However, the mechanisms by which this attenuated SIV vaccine works do not seem to be through known immune responses (such as antibodies). Rather, protection is postulated to be mediated by evolutionary conserved mechanisms, designated innate immunity. Although such an attenuated SIV/HIV virus is dangerous and would never be used to vaccinate humans, knowing how it works would be very useful to design an HIV vaccine. The aim of our project is to study the mechanisms of protection by an attenuated HIV and SIV, in order to get insights on how to design a non-dangerous and potent HIV vaccine. We intend to carry out these experiments in the mouse because the same innate immunity as in monkeys and humans is likely to be effective, if indeed, this represents the mode of protection. Moreover, mice offer strong genetic tools to dissect this protective effect. Transgenic mice expressing the attenuated HIV or SIV will be challenged with HIV or SIV, in order to determine whether protection also arise in mice and by which mechanism.