A team led by the Duke Human Vaccine Institute (DHVI) has developed a vaccine approach that works like a GPS, guiding the immune system through specific steps to produce broadly neutralizing antibodies against HIV.
Publication in the magazine. Cellular host and microbeThe study describes an approach that provides step-by-step instructions for the immune system to generate the elusive but necessary antibodies for a successful HIV vaccine.
“HIV is the most rapidly evolving virus known. Therefore, a long-standing goal in HIV research is to create a vaccine that can generate broadly neutralizing antibodies that can recognize various strains of HIV,” the author said. principal Kevin Wiehe, Ph.D. associate professor in the Department of Medicine at Duke University School of Medicine and director of research at DHVI.
Wiehe and his colleagues started with an engineered version of a broadly neutralizing antibody in its native state, before any mutations occurred. Knowing that the antibody will need to mutate to keep up with the ever-changing HIV virus, the researchers added sequential mutations one by one to determine which mutations were essential for the antibody to broadly neutralize HIV.
Doing this allowed them to figure out what the exact points were along the path to arriving at broadly neutralizing antibodies. They then developed a vaccine that gave the immune system step-by-step instructions to follow that mutational pathway.
Using mice specially bred to encode the original version of the antibody, the researchers showed that the guidance system approach caused the immune system to begin churning out the targeted antibodies.
“This paper shows that our mutation-guided vaccine strategy can work,” Wiehe said, adding that the technique could also be used in vaccines for other diseases. “This strategy potentially gives us a way to design vaccines to direct the immune system to produce whatever antibody we want, which could be a broadly neutralizing antibody to all coronavirus variants, or an anti-cancer antibody.”
Wiehe said the next challenge will be to reproduce the study in primates and then in humans.
In addition to Wiehe, study authors include Kevin O. Saunders, Victoria Stalls, Derek W. Cain, Sravani Venkatayogi, Joshua S. Martin Beem, Madison Berry, Tyler Evangelous, Rory Henderson, Bhavna Hora, Shi-Mao Xia, Chuancang Jiang, Amanda Newman, Cindy Bowman, Xiaozhi Lu, Mary E. Bryan, Joena Bal, Aja Sanzone, Haiyan Chen, Amanda Eaton, Mark A. Tomai, Christopher B. Fox, Ying Tam, Christopher Barbosa, Mattia Bonsignori, Hiromi Muramatsu, S. Manir Alam, David Montefiori, Wilton B. Williams, Norbert Pardi, Ming Tian, Drew Weissman, Frederick W. Alt, Priyamvada Acharya and Barton F. Haynes.
The study received financial support from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (UM1AI144371, 1U19AI135902-01, P01AI131251-01).