New HIV Vaccine Target Could Solve Mutation Problem

Main Category: HIV / AIDS
Also Included In: Immune System / Vaccines
Article Date: 08 Nov 2007 - 17:00 PDT

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Researchers at UCSF and the University of Toronto have identified a potential new way of fighting against HIV infection that relies on the remnants of ancient viruses, human endogenous retroviruses (HERV), which have become part of the genome of every human cell.

Researchers believe that their findings, publishing on November 9, 2007 in the journal PLoS Pathogens, could lead to a vaccine targeting HERV that kills HIV infected cells.

Mounting evidence suggests that HIV infection could enable HERV expression by disrupting the normal controls that keep HERV in check. In some HIV-infected individuals, infection fighting T cells are able to target HERV expressing cells.

"One important limitation to a T-cell vaccine targeting HIV itself is that HIV exists in so many variations and is constantly mutating. If we can find other ways for the immune system to target HIV-infected cells, we can overcome this problem in making an HIV vaccine. HERV may provide us with a good target to test," said study co-author, Dr. Keith E. Garrison.

HERV, human endogenous retroviruses, are the genomic fossils left behind from ancient viral infections that exist largely dormant within every cell. While HERV are present in every cell, HIV may disrupt the normal constraints on HERV activity as it alters the cell to produce more HIV. This led the authors of the study to look for T cell responses to HERV in HIV-positive people. They found T cell responses to HERV in HIV-positive people that were not present in HIV-negative people.

The researchers also compared the T cells that recognize HERV to other types of T cells, including those that recognize HIV. They found that T cells recognizing HERV were different from T cells that recognize HIV.

"HIV is poorly contained by the immune system, resulting in disease progression in most people. In contrast, infection with cytomegalovirus (CMV) is generally controlled for life. HERV specific T cells have more features in common with T cells that kill CMV, than with T cells that kill HIV. This is an encouraging finding which suggests that HERV specific T cells may be more effective than HIV specific T cells in controlling virus," said study co-author, Brad Jones.

The researchers looked at 29 individuals recently infected with HIV from the UCSF OPTIONS Project, 13 HIV-negative individuals and 3 hepatitis-C-infected, HIV-negative individuals. In the group recently infected with HIV, researchers found a relationship between the degrees of T-cell response to HERV and the levels of HIV virus present in their blood.

"Although these results are preliminary, they encourage new ways to make the immune system potentially target HIV infected cells," said study co-author Prof. Mario A. Ostrowski from the University of Toronto.

Researchers believe that a vaccine could be created containing HERV antigens that would stimulate T-cells targeting cells expressing HERV. Although the vaccine would not produce T cells capable of recognizing HIV itself, it would evoke a cellular immune response that could still protect people from becoming infected or limit the extent of damage caused by HIV.

"These findings may lead to new lines of attack against HIV, and the clue came from the study of the viruses within us," said study co-author, Prof. Douglas F. Nixon from UCSF.

The research was supported by funds from the J. David Gladstone Institutes, the AIDS Research Institute at UCSF, the Irvington Institute and the Canadian Institutes of Health Research.

CITATION: Garrison KE, Jones RB, Meiklejohn DA, Anwar N, Ndhlovu LC, et al. (2007) T cell responses to human endogenous retroviruses in HIV-1 infection. PLoS Pathog 3(11): e165. doi:10.1371/journal.ppat.0030165
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