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