The very immune cells that HIV vaccines aim to increase may already have been affected by the virus, a reason why AIDS vaccines have backfired in more than one clinical trial, a study says.
The findings show the unique challenges that HIV poses in terms of vaccine development.
“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,” explained senior author Guido Silvestri from Emory University, Georgia, in the US.
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. While CD8 is a marker for “killer” cells, 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.
In this study, researchers immunised monkeys with five different combinations of vaccines encoding SIV proteins.
SIV infected primates may experience AIDS-like illness in humans.
The monkeys received an initial immunisation followed by two booster shots after 16 and 32 weeks.
But the immunisation regimens did not prevent SIV infection. The monkeys that became infected had higher levels of activated CD4+T cells in rectal biopsies before challenge, Silvestri added.
“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 explained.
The findings were published in the journal Proceedings of the National Academy of Sciences.
Diane G. Carnathan, Katherine S. Wetzel, Joana Yu, S. Thera Lee, Brent A. Johnson, Mirko Paiardini, Jian Yan, Matthew P. Morrow, Niranjan Y. Sardesai, David B. Weiner, Hildegund C. J. Ertl, and Guido Silvestri. Activated CD4+CCR5+ T cells in the rectum predict increased SIV acquisition in SIVGag/Tat-vaccinated rhesus macaques. PNAS 2014 ; published ahead of print December 30, 2014, doi:10.1073/pnas.1407466112