Time and again, HIV vaccine trials have proved right the dictum, ‘monkeys lie and mice do not always tell the truth'. Positive results in animals did not translate into good outcome in humans. However, the results of a recent study in rhesus monkeys show greater promise of protective effects getting replicated in humans. The study was published in Nature (“Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys,” by Dan H. Barouch et al.). Monkeys get infected not with HIV but only with simian immunodeficiency virus (SIV), which is distantly related to its human counterpart. So the monkeys were primed with SIV vaccine and then given a boost six months later. Vaccines with different combinations of genetically engineered SIV genes were tested. At the end of one year after priming, the animals were exposed to the virus six times. While 75 per cent of animals that did not receive a vaccine (control group) got infected after the first exposure, only 12 per cent of those that received the best vaccine did. And, at the end of six exposures, while all the controls got infected, only a majority of the vaccinated monkeys did. The best vaccine produced 80 per cent reduction in the “probability” of infection per exposure. Most importantly, the trial proved its ability to produce partial protection against a virulent, tough-to-neutralise strain that is different from the one used in making the vaccine.
Aside from protecting the monkeys, the vaccine was also effective in reducing the viral load in those infected. Although the precise mechanism responsible for preventing SIV infection is yet to be determined, the requirements for achieving the primary endpoint in monkeys have been found to be very different from those for reducing the viral load. Only those animals that produced high levels of ‘envelope' antibodies (in response to the Env antigen in the vaccine) remained free of infection. So critical was the inclusion of the Env antigen that the protection conferred was extended even to the virus that differed from the vaccine strain. Different immune responses against the ‘envelope' antigen and another antigen (Gag) were responsible for reducing the viral load. Incidentally, the importance of Env antigen was brought out earlier by the 2009 human Phase III Thai trial (RV144), which produced modest protection of 31 per cent. Volunteers who had produced high levels of antibodies against the Env antigen remained infection-free. There is room for cautious optimism that designing an effective HIV vaccine may become possible if the vital clues from the latest study are wisely utilised.
Keywords: HIV vaccine