A reason some failed HIV vaccines actually increased the risk of acquiring the virus appears to be that they led to greater levels of the very immune cells HIV targets. Publishing their findings in the Proceedings of the National Academy of Sciences, researchers tested five different combinations of vaccines in rhesus macaque monkeys in order to understand why they failed.

These vaccines were designed to prompt an immune response driven by immune cells as opposed to neutralizing antibodies. In this “reductionist approach,” the vaccines encoded various proteins of SIV, HIV’s simian cousin, that are only found inside the virus.

The primates received the vaccine and then booster shots after 16 and 32 weeks. Then the researchers rectally exposed them to SIV once a week for up to 15 weeks. For the most part, the vaccines failed to prevent SIV acquisition. All of the immunized monkeys had detectable levels of circulating CD8, or “killer” cells, which might have offered protection against the virus. However, there was no link between the cells’ presence and any actual protection.

The monkeys that contracted the virus had greater levels of activated CD4 cells in their rectal biopsies before rectal exposure to the virus.

“This study shows that if a vaccine induces high levels of activated [CD4] cells in mucosal tissues, any potential protective effect of the vaccine may be hampered,” senior author Guido Silvestri, MD, chief of microbiology and immunology at Yerkes National Primate Research Center, said in a press release.

To read the press release, click here.

To read the study abstract, click here.