For decades, scientists have chased a daunting HIV vaccine goal: teaching the immune system to make rare antibodies capable of stopping the HIV virus’s many forms.
Now researchers at the University of Pennsylvania and Duke Human Vaccine Institute (DHVI) report a major step toward that goal, and the strategy has already advanced to Phase 1 clinical trials.
In a study published in Nature, the team describes an experimental vaccine approach that rapidly generated broad, potent HIV-fighting antibodies.
“The reproducibility and the pace of these antibody responses suggests that this vaccine candidate could become a component of a practical AIDS vaccine,” said study co-author Kshitij Wagh, PhD, of Duke University School of Medicine, who helped develop the patented strategy.
The work centers on a computational method called neutralization signature analysis, developed by Wagh, and Bette Korber, PhD, of Los Alamos National Laboratory. The approach emerged from the Consortia of HIV/AIDS Vaccine Development (CHAVD), a National Institute of Allergy and Infectious Diseases-supported research network led by DHVI’s Barton Haynes, MD.
Instead of using naturally occurring HIV proteins and waiting to see whether they produce protective antibodies, researchers designed vaccine targets with the help of computer models, selecting viral features most likely to train the immune system to recognize and block HIV, the virus that causes AIDS.
At Penn, researchers used selected sequences to create mRNA vaccines, while Duke’s, Kevin O. Saunders, PhD, incorporated them into protein nanoparticles for a multi-part vaccine used in preclinical vaccine trials.
The results exceeded expectations. Using an antibody analysis tool developed by Haynes, researchers detected broadly neutralizing antibodies after just two vaccine doses.
After a third shot, more than 90% of the vaccinated subjects produced immune responses capable of neutralizing a wide range of HIV variants.
That speed is especially striking because similar antibodies can take years to develop during natural HIV infection, if they appear at all.
The clinical trials will evaluate if the vaccine is safe and could help protect against HIV in people.