DURHAM, N.C. -- Building on insights from an HIV vaccine regimen in humans that had partial success during a phase 3 clinical trial in Thailand, a Duke-led research team used a more-is-better approach in monkeys that appeared to improve vaccine protection from an HIV-like virus.
Adding three more targets to the investigational vaccine, for a total of five, protected more than half of the vaccinated animals from simian-human immunodeficiency virus infection.
"The vaccine regimen tested in the Thai trial, known as RV144, had 31-percent efficacy and is the only HIV investigational vaccine regimen to have demonstrated even modest protection from HIV infection," said Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute and senior author of a study published online June 8 in the journal Nature Communications. "In this study in monkeys, we increased that level of protection to 55 percent by using a pentavalent (five-part) vaccine."
Haynes and colleagues -- including Bette T. Korber of the Los Alamos National Laboratory, who led the vaccine design -- started from the foundation used in the RV144 human vaccine trial in Thailand, adding targets that elicited antibody responses to regions of the HIV envelope.
Those antibodies were fairly easy to induce, Haynes said. By adding the three additional regions of the viral envelope to the investigational vaccine, the researchers improved the level of protection afforded to animals exposed to a difficult-to-neutralize strain of the simian virus, which is comparable to HIV.
"Vaccine protection using this model of virus infection in primates is possible," said lead author Todd Bradley, Ph.D., a member of the Duke Human Vaccine Institute. "This is a proof-of-concept that provides a strategy to improve upon the first HIV vaccine regimen that provided limited protection in people."
Bradley and Haynes said additional research will try to identify whether all or just one of the additional targets to the viral envelope generated the added protection.
In addition to Bradley and Haynes, study authors from Duke include Justin Pollara, Nathan Vandergrift, Xiaoying Shen, Robert Parks, Derrick Goodman, Amanda Eaton, Kevin O. Saunders, Richard Scearce, Laura L. Sutherland, David C. Montefiori, Anthony Moody, Hua-Xin Liao, Georgia Tomaras and Guido Ferrari.
They were joined by Korber, along with Sampa Santra, Harikrishnan Balachandran and Linh V. Mach of Harvard University; Srivamshi Pittala, Chris Bailey-Kellogg, Joshua A. Weiner and Margaret E. Ackerman of Dartmouth College; Sanjay Phogat and James Tartaglia of Sanofi Pasteur; Steven G. Reed of Infectious Disease Research Institute; Shiu-Lok Hu of University of Washington; James F. Theis and Abraham Pinter of Rutgers University; Thomas B. Kepler of Boston University; Kristina K. Peachman of Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine; Mangala Rao and Nelson L. Michael of Walter Reed Army Institute of Research; and Todd J. Suscovich and Galit Alter of Ragon Institute of MGH, MIT and Harvard.
The study received funding support from the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant (UMI-AI100645) from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and a Collaboration for AIDS Vaccine Discovery Grant (OPP1033098) from the Bill & Melinda Gates Foundation.