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Study explains ‘backfire’ effect

Clinical trials have shown that HIV vaccines can "backfire" and lead to increased rates of infection. Now, a new study published suggests an explanation for this backfire effect, reports Medical News Today. Senior author of the new study, Guido Silvestri, chief of microbiology and immunology at Yerkes National Primate Research Centre at Emory University in Atlanta, says: "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."

Research into developing vaccines for HIV/Aids has largely focused on stimulating antiviral T cells.

Of the two main groups of T cells, CD4+ T cells are "helper" cells known to be targets for HIV and its non-human primate equivalent simian immunodeficiency virus (SIV), while CD8+ T cells are "killer" cells that some studies have suggested may be valuable in controlling infection.

Silvestri and colleagues immunised rhesus macaques with five different combinations of SIV vaccines. The monkeys received booster shots following their initial immunisation at 16 and 32 weeks.

The vaccines in the study deviated from the norm for SIV vaccines because they encode the SIV proteins on the inside of the virus only. The researchers did this as part of what they call a "reductionist approach," to test the effects of cell immunity to the virus without stimulating the production of neutralising antibodies.

Following immunisation, the rectums of the monkeys were exposed to SIV once per week, up to 15 times in total. The team found that the immunisation did not generally prevent SIV infection. Although "killer" CD8+ T cells were detected circulating in all the immunized monkeys, the researchers found no correlation between these levels of CD8+ cells and reduced likelihood of infection.

However, the team do report one important finding – the monkeys that became infected exhibited higher levels of activated CD4+ T cells in rectal biopsies prior to infection.

"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," Silvestri explains.

The take-home message from this study, the researchers say, is that HIV vaccine developers should pursue concepts and products that provoke a strong antiviral immune response without increasing the number of "helper" CD4+ T cells in portals of entry for the virus.

[link url="http://www.medicalnewstoday.com/articles/287572.php"]Full Medical News Today report[/link]
[link url="http://www.pnas.org/content/early/2014/12/30/1407466112.abstract?sid=42e15bfa-a8f8-4f2c-b635-1ca4c21e4d8b"]Proceedings of the National Academy of Sciences abstract[/link]

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