A vaccine has been found that blocks the monkey equivalent of HIV. The discovery works in the opposite way to normal vaccines, but its relatively simple structure may lead to an effective oral vaccine for humans.
Simian immunodeficiency viruses (SIVs) are close relatives of HIV which infect various non-human primates, such as chimpanzees and sooty mangabeys. Unlike HIV, these viruses do not usually cause disease in their hosts; however, rhesus macaques are vulnerable to SIV and develop a disease that is pathologically similar to humans infected with HIV. These monkeys are therefore a useful model for HIV/AIDS research.
In both rhesus monkeys and humans, the virus predominantly infects and replicates inside cells of the immune system, in particular a type of white blood cell called a CD4+ T cell. These cells are normally a crucial part of our resistance to disease and thus their depletion leaves infected individuals susceptible to infections with other pathogens.
Macaques given the new vaccine produce a previously unknown type of regulatory CD8 white blood cell that prevents infected CD4 cells from becoming activated. Since resting (non-activated) CD4 cells are largely non-permissive for viral replication, this failure to activate blocked SIV from being able to make new viral particles. Subsequently, the monkeys were protected from a challenge infection with SIV.
The vaccine involved a combination of inactivated SIV and bacteria. The first trials used BCG, often used as a vaccine against tuberculosis. However, researchers at Paris-Descartes University replicated the effect with gut bacteria used in probiotic supplements—if the same technique works in humans you might get your cravings for unhealthy food fixed at the same time as being protected against infection.
Trials are being planned to see if people without HIV have the same immune response. A more advanced trial would see HIV infected individuals undergoing treatment given the vaccine. If their response suggests the vaccine is working then they could be taken off antiretroviral treatment to see if the virus remains suppressed.
Jean-Marie Andrieu, lead author of the Frontiers in Immunology paper that announced the finding, says the idea of suppressing a response to HIV—rather than stimulating it as most vaccines do—is an old one. However, no one expected it to work so well after other paths either failed or were too expensive for widespread use.
BCG was chosen because it is known to bind to dendritic cells infected by HIV, while the immune system recognizes gut bacteria as not being a threat and avoids attacking them. It seems that either acted as a passport for the inactivated SIV.
Of the 29 monkeys given the vaccine, 15 appear to have complete and long-lasting protection against SIV. Oral administration, besides being much easier, appears to be more effective than vaginal or rectal application. Injections had the least success.
When the macaques were given an antibody to the CD8 cells their protection disappeared, but encouragingly, it returned when the antibodies were withdrawn.
If the same pattern is seen in humans, the vaccine would not only stop people getting HIV, but could work as therapy for those already infected.
Surprisingly, given the enormous public interest in the topic, two months passed between the paper's publication and it being noticed by Aidsmap.
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