Vaccine candidate spurs elusive type of broadly neutralizing HIV antibodies

An HIV vaccine candidate developed at the Duke Human Vaccine Institute triggered low levels of an elusive type of broadly neutralizing HIV antibodies among a small group of people enrolled in a 2019 clinical trial.

The finding, reported May 17 in the journal Cell, not only provides proof that a vaccine can elicit these antibodies to fight diverse strains of HIV, but that it can also initiate the process within weeks, setting in motion an essential immune response.

The vaccine candidate targets an area on the HIV-1 outer envelope called the membrane proximal external region (MPER), which remains stable even as the virus mutates. Antibodies against this stable region in the HIV outer coat can block infection by many different circulating strains of HIV.

This work is a major step forward as it shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV. Our next steps are to induce more potent neutralizing antibodies against other sites on HIV to prevent virus escape. We are not there yet, but the way forward is now much clearer."

Barton F. Haynes, M.D., senior author, director of the Duke Human Vaccine Institute (DHVI)

The research team analyzed data from a phase 1 clinical trial of a vaccine candidate developed by Haynes and S. Munir Alam, Ph.D., at DHVI.

Twenty healthy, HIV-negative people enrolled in the trial. Fifteen participants received two of four planned doses of the investigational vaccine, and five received three doses.

After just two immunizations, the vaccine had a 95% serum response rate and a 100% blood CD4+ T-cell response rate -- two key measurements that demonstrated strong immune activation. Most of the serum responses mapped to the portion of the virus targeted by the vaccine.

Importantly, broadly neutralizing antibodies were induced after just two doses.

The trial was halted when one participant experienced a non-life-threatening allergic reaction, similar to rare incidences reported with COVID-19 vaccinations. The team investigated the cause of the event, which was likely from an additive.

"To get a broadly neutralizing antibody, a series of events needs to happen, and it typically takes several years post-infection," said lead author Wilton Williams, Ph.D., associate professor in Duke's Department of Surgery and member of DHVI. "The challenge has always been to recreate the necessary events in a shorter space of time using a vaccine. It was very exciting to see that, with this vaccine molecule, we could actually get neutralizing antibodies to emerge within weeks."

Other features of the vaccine were also promising, most notably how the crucial immune cells remained in a state of development that allowed them to continue acquiring mutations, so they could evolve along with the ever-changing virus.

The researchers said there is more work to be done to create a more robust response, and to target more regions of the virus envelope. A successful HIV vaccine will likely have at least three components, all aimed at distinct regions of the virus.

"Ultimately, we will need to hit all the sites on the envelope that are vulnerable so that the virus cannot escape," Haynes said. "But this study demonstrates that broadly neutralizing antibodies can indeed be induced in humans by vaccination. Now that we know that induction is possible, we can replicate what we have done here with immunogens that target the other vulnerable sites on the virus envelope."

In addition to Haynes and Williams, study authors include S. Munir Alam, Gilad Ofek, Nathaniel Erdmann, David Montefiori, Michael S. Seaman, Kshitij Wagh, Bette Korber, Robert J. Edwards, Katayoun Mansouri, Amanda Eaton, Derek W. Cain, Mitchell Martin, Robert Parks, Maggie Barr, Andrew Foulger, Kara Anasti, Parth Patel, Salam Sammour, Ruth J. Parsons, Xiao Huang, Jared Lindenberger, Susan Fetics, Katarzyna Janowska, Aurelie Niyongabo, Benjamin M. Janus, Anagh Astavans, Christopher B. Fox, Ipsita Mohanty, Tyler Evangelous, Yue Chen, Madison Berry, Helene Kirshner, Elizabeth Van Itallie, Kevin Saunders, Kevin Wiehe, Kristen W. Cohen, M. Juliana McElrath, Lawrence Corey, Priyamvada Acharya, Stephen R. Walsh, and Lindsey R. Baden.

The study received funding support from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (AI100645, AI144371, AI170752), and from the Bill & Melinda Gates Foundation (OPP1094352/INV-007688).

The content of this press release is solely the responsibility of DHVI and does not necessarily represent the official views of the National Institutes of Health.

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