Serum-neutralizing antibody titers correlate strongly with protection against SHIV infection

MADRID, SPAIN – OCTOBER 24, 2018

Results from a meta-analysis combining information from a variety of nonhuman primate SHIV (simian/human immunodeficiency virus) challenge studies suggest that the concentration of neutralizing HIV antibodies in the bloodstream correlates strongly to protection against SHIV infection. The data analyzed originated from 12 published and 5 unpublished SHIV challenge studies spanning 2010–2017, which focused on seven SHIV strains and 16 broadly neutralizing monoclonal antibodies (bnAbs) targeting five envelope epitope regions. In each challenge study, primates were infused with a single bnAb to neutralize SHIV.

Researchers used data from the previous SHIV studies to estimate the dilution level of antibody at which 50% of SHIV would be neutralized, i.e. the serum 50 percent neutralization titer or inhibitory dilution (ID50). Across all experimental factors, including epitope category, challenge virus, dose and sex, administering a serum-neutralizing ID50 titer strongly correlated with protection against SHIV infection. For every ten-fold increase in ID50 titer, the study authors found around 95 percent reduction in the odds of SHIV infection, suggesting that the measurement of serum neutralizing titers is a key factor in bnAb clinical efficacy trials and in evaluation of vaccines designed to elicit neutralizing antibodies.

“Characterizing the relationship between neutralizing antibody titers and the level of protection in nonhuman primate challenge studies will be helpful in understanding and predicting the efficacy of bnAbs in human trials. Our analyses suggest that serum-neutralizing antibody titers are strong correlates of protection against SHIV infection,” said Ying Huang, Ph.D., associate member in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center.

The study was a collaboration between Fred Hutchinson Cancer Research Center, the Vaccine Research Center of the NIH and the Scripps Center for HIV/AIDS Immunology and Immunogen Discovery (CHAVI-ID). “The neutralizing antibody titers that Ying has determined are also important to give us an estimate of what we are shooting for from an HIV vaccine,” commented Dennis Burton, Director of CHAVI-ID.

Importance of the meta-analysis results to the Antibody Mediated Prevention (AMP) studies
VRC01, an antibody initially identified in an individual infected with HIV for over 10 years but who had never developed AIDS, has been shown to block over 90 percent of tested HIV strains, and was advanced to trials in humans. The AMP studies, which commenced in 2016, aim to assess VRC01’s ability to prevent HIV by comparing HIV infection rates in 4,600 volunteers at high risk of acquiring HIV infection, who receive varying amounts of VRC01 or a placebo. The meta-analysis results reaffirm the importance of analyzing the measurement of serum-neutralizing titers against HIV.

Though much remains to be accomplished in the field of HIV vaccine research, HVTN researchers are making bold strides in their pursuit to find a safe and effective HIV vaccine.

We are on a scientific journey to find a safe and effective HIV vaccine to prevent new HIV infections in the future
An estimated 35 million lives have been lost since the HIV/AIDS pandemic began more than three decades ago.  The World Health Organization (WHO) estimated that 37.6 million people were living with HIV in 2016, and 1.8 million new infections were documented in the same year. There are an estimated 5,000 new HIV infections daily around the world.  Key populations at risk of acquiring HIV, irrespective of epidemic type or local context, include men who have sex with men, people in prisons and other closed settings, sex workers and their clients, transgender people and people who inject drugs.

The HVTN is the world’s largest publicly funded collaboration facilitating the development of vaccines to prevent HIV/AIDS and has together with global partners demonstrated significant scientific progress in pursuit of an effective HIV vaccine.  Through an inclusive strategy, and by forging in-country relationships on four continents at 44 clinical trial sites, the network, headquartered at the Fred Hutchinson Cancer Research Center, works collaboratively with global communities and partners in the search for an effective HIV vaccine.  Primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), the network currently manages 18 active clinical trials of which three are large-scale in-human efficacy trials.


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About Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.

 

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