Why Some HIV Vaccines Backfire

Because vaccines can increase the number of immune cells that serve as viral targets, some designed to protect against HIV can actually lead to increased rates of infection.

The findings suggest that when evaluating potential HIV/AIDS vaccines, researchers may need to steer away from those that activate too many viral target cells in mucosal tissues.

“One of the reasons why it has been so difficult to make an AIDS vaccine is that the virus infects the very cells of the immune system that any vaccine is supposed to induce,” says senior author Guido Silvestri, professor of pathology and laboratory medicine at Emory University.

T CELLS

A large part of the HIV/AIDS vaccine effort has been focused on developing vaccines that stimulate antiviral T cells.

T cells come in two main categories, defined by the molecules found on their surfaces. CD8 is a marker for “killer” cells, while CD4 is a marker for “helper” cells.

CD4+ T cells are known to be primary targets for HIV and SIV (simian immunodeficiency virus) infection, while several studies have proposed that CD8+ T cells could be valuable in controlling infection.

VACCINATED MONKEYS

For the new study, published in the Proceedings of the National Academy of Sciences, researchers immunized rhesus macaques with five different combinations of vaccines encoding SIV proteins found on the inside of the virus only.

This experimental strategy was designed to examine the effects of cell-mediated immunity, without stimulating the production of neutralizing antibodies, in what scientists refer to as a “reductionist approach.”

The monkeys received an initial immunization followed by two booster shots after 16 and 32 weeks. They were then exposed to repeated low-dose intrarectal challenge with SIV, once per week, up to 15 times.

In general, the immunization regimens did not prevent SIV infection. While all the immunized monkeys had detectable levels of circulating “killer” CD8+ T cells, there was no correlation between these cells and preventing infection.

The most important result, however, is that the monkeys that became infected had higher levels of activated CD4+T cells in rectal biopsies before challenge, Silvestri says.

“This study shows that if a vaccine induces high levels of activated CD4+ T cells in mucosal tissues, any potential protective effect of the vaccine may be hampered,” he says.

Researchers from the University of Pennsylvania, the Wistar Institute, and Inovio Pharmaceuticals contributed to the study.

The National Institute of Allergy and Infectious diseases and the National Institutes of Health Director’s Office of Research Infrastructure Programs provided funding for the research.