HIV Vaccines Should Avoid Viral Target Cells, Primate Model Study Suggests

Article

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 at Emory University, have newly published results that support a straightforward explanation for the backfire effect: vaccination may increase the number of immune cells that serve as viral targets. In a nonhuman primate model of HIV transmission, higher levels of viral target cells 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 vaccine 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 cells in the portals of entry for the virus.

Source: Emory University

Recent Videos
Pathogen Playbook Presenter: Sharon Ward-Fore, BS, MS, MT(ASCP), CIC, FAPIC
Mark Wiencek, PhD
Rebecca Crapanzano-Sigafoos, DrPH, CIC, AL-CIP, FAPIC
The CDC’s updated hospital respiratory reporting requirement has added new layers of responsibility for infection preventionists. Karen Jones, MPH, RN, CIC, FAPIC, clinical program manager at Wolters Kluwer, breaks down what it means and how IPs can adapt.
Studying for the CIC using a digital tablet and computer (Adobe Stock 335828989 by NIKCOA)
Infection Control Today's Conversations with the HSPA President, Arlene Bush, CRCST, CER, CIS, SME, DSMD, CRMST
Infection Control Today's Conversations with the HSPA President, Arlene Bush, CRCST, CER, CIS, SME, DSMD, CRMST
Cheron Rojo, BS, FCS, CHL,  CER, CFER, CRCST
Matthias Tschoerner, Dr Sc
Standardizing Cleaning and Disinfection
Related Content