HIV vaccines should avoid viral target cells, primate model study suggests

January 2, 2015

Vaccines designed to protect against HIV can backfire and lead to increased rates of infection. This unfortunate effect has been seen in more than one vaccine clinical trial.

Scientists at Yerkes National Primate Research Center, Emory University, have newly published results that support a straightforward explanation for the backfire effect: vaccination may increase the number of that serve as viral targets. In a nonhuman primate model of HIV transmission, higher levels of viral in gateway mucosal tissues were associated with an increased risk of infection.

The findings, published in Proceedings of the National Academy of Sciences, suggest that researchers, when evaluating potential HIV/AIDS vaccines, 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, chief of microbiology and immunology at Yerkes National Primate Research Center.

Silvestri is also a professor of pathology and laboratory medicine at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. The first author of the paper is senior research specialist Diane Carnathan, PhD, and colleagues from the Wistar Institute, Inovio Pharmaceuticals and the University of Pennsylvania contributed to the study.

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.

In this study, 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. The monkeys 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, was 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 explains.

The study emphasizes the unique challenges that HIV poses in terms of vaccine development, and the importance of pursuing vaccine concepts and products that elicit strong antiviral immune responses without increasing the number of CD4+ T in the portals of entry for the virus.

Explore further: Immune cells proposed as HIV hideout don't last in primate model

More information: Proceedings of the National Academy of Sciences, www.pnas.org/content/early/201 … /1407466112.abstract

Related Stories

Immune cells proposed as HIV hideout don't last in primate model

October 31, 2014
Where does HIV hide? Antiretroviral drugs can usually control the virus, but can't completely eliminate it. So any strategy to eradicate HIV from the body has to take into account not only the main group of immune cells the ...

Antibodies help protect monkeys from HIV-like virus, scientists show

May 5, 2011
Using a monkey model of AIDS, scientists have identified a vaccine-generated immune-system response that correlates with protection against infection by the monkey version of HIV, called simian immunodeficiency virus (SIV). ...

Masking HIV target cells prevents viral transmission in animal model

November 24, 2014
Cloaking immune cells with antibodies that block T cell trafficking to the gut can substantially reduce the risk of viral transmission in a non-human primate model of HIV infection, scientists report.

How llamas' unusual antibodies might help in the fight against HIV/AIDS

December 18, 2014
Most vaccines work by inducing an immune response characterized by neutralizing antibodies against the respective pathogen. An effective HIV vaccine has remained elusive so far, but researchers have continued to make progress, ...

Penile foreskin is immunologically complete: raises new vaccine possibilities for HIV vaccine

July 23, 2012
Rhesus macaque monkeys infected with simian immunodeficiency virus (SIV) harbor immunoglobulin G (IgG) and SIV-specific antibodies and T cells in the foreskin of the penis, according to a study in the July 2012 Journal of ...

Animal vaccine study yields insights that may advance HIV vaccine research

December 18, 2013
A vaccine study in monkeys designed to identify measurable signs that the animals were protected from infection by SIV, the monkey version of HIV, as well as the mechanism of such protection has yielded numerous insights ...

Recommended for you

New injectable antiretroviral treatment proved to be as effective as standard oral therapy

August 3, 2017
Intramuscularly administered antiretroviral therapy (ART) may be as effective for HIV treatment as current oral therapies. This is the main conclusion of a Phase II clinical trial carried out by 50 research centers around ...

Research finds home-based kit would increase HIV testing

July 31, 2017
Research led by William Robinson, PhD, Associate Research Professor of Behavioral & Community Health Sciences at LSU Health New Orleans School of Public Health, has found that 86% of heterosexuals who are at high risk for ...

Scientists divulge latest in HIV prevention

July 25, 2017
A far cry from the 1990s "ABC" campaign promoting abstinence and monogamy as HIV protection, scientists reported on new approaches Tuesday allowing people to have all the safe sex they want.

Girl's HIV infection seems under control without AIDS drugs

July 24, 2017
A South African girl born with the AIDS virus has kept her infection suppressed for more than eight years after stopping anti-HIV medicines—more evidence that early treatment can occasionally cause a long remission that, ...

Meds by monthly injection might revolutionize HIV care (Update)

July 24, 2017
Getting a shot of medication to control HIV every month or two instead of having to take pills every day could transform the way the virus is kept at bay.

Candidate AIDS vaccine passes early test

July 24, 2017
The three-decade-old quest for an AIDS vaccine received a shot of hope Monday when developers announced that a prototype triggered the immune system in an early phase of human trials.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.