Preventative HIV Vaccine Candidate Triggers Desired Immune Responses in Humans, and Protects from Infection in Pre-Clinical Trials

BOSTON – More than three decades after the identification of the human immunodeficiency virus (HIV), scientists are still working to develop a preventative vaccine that could finally put an end to the epidemic for which there are nearly two million new infections each year.

In a new study, published July 6 in The Lancet, a team of researchers led by Beth Israel Deaconess Medical Center’s Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research in collaboration with Janssen Vaccines & Prevention and other partners, evaluated a series of preventative HIV vaccine regimens in uninfected human volunteers in five countries. In a similarly designed study, Barouch and colleagues tested the same vaccine for its ability to protect rhesus monkeys challenged with an HIV-like virus from infection. The findings showed the vaccines induced robust and comparable immune responses in humans and monkeys and protected monkeys against acquisition of infection.

“This study demonstrates that the mosaic Ad26/Ad26 plus gp140 vaccine candidate induced robust and comparable immune responses in human and monkeys,” said Barouch, who is also Professor of Medicine at Harvard Medical School. “Moreover, the vaccine provided 67 percent protection against viral challenge in monkeys.”

Intended to provide broad protection from the many strains of HIV that are prevalent worldwide, the “mosaic” vaccine contains a patchwork of genetic sequences found among various HIV strains. Known as APPROACH, the phase 1/2a trial tested seven different Ad26/Env HIV vaccine regimens for their safety, tolerability and the ability to elicit immune responses in 393 healthy adult volunteers in Rwanda, South Africa, Thailand, Uganda and the United States. All vaccine regimens were well-tolerated and induced robust immune responses in the participants.

“Based on these data, the mosaic Ad26/Env HIV-1 vaccine has been advanced into a phase 2b clinical efficacy study to determine whether this vaccine will prevent HIV infection in humans in southern Africa,” said Barouch. “We expect results in 2021. This is only the 5th HIV vaccine concept that will be tested for efficacy in humans in the 35+ year history of the global HIV epidemic."

The study is the result of a collaboration among researchers at BIDMC, Harvard Medical School and the Ragon Institute of Massachusetts General Hospital, MIT and Harvard; the United States Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research (WRAIR); the National Institute of Allergy and Infectious Diseases (NIAID); the International AIDS Vaccine Initiative; the HIV Vaccine Trials Network (HVTN), Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson; and multiple other partners. 

In addition to Barouch, co-authors include Lauren Peter, Joseph P Nkolola, Erica N. Borducci, Abishek Chandrashekar, David Jetton, and Kathryn E. Stephenson of Beth Israel Deaconess Medical Center; Galit Alter, of the Ragon Institute of MGH, MIT and Harvard; co-lead author Frank L. Tomaka, of Janssen Research and Development; co-lead author Frank Wegmann, Daniel J. Stieh, Jerald Sadoff, Lorenz Scheppler, Mo Weijtens, Karin Feddes-de Boer, Daniëlle van Manen, Jessica Vreugdenhil, Roland Zahn, Jeroen Tolboom, Jenny Hendriks, Zelda Euler, Maria G. Pau, Hanneke Schuitemaker of Janssen Vaccine & Prevention BV; Merlin L. Robb and Nelson L. Michael, of the Military HIV Research Program, Walter Reed Army Institute of Research; Wenjun Li of University of Massachusetts Medical School; Bette Korber of Los Alamos National Laboratory; Georgia D.Tomaras, David C. Montefiori, Erika Lazarus and Fatima Laher of Duke University; Glenda Gray, University of Witwatersrand; Nicole Frahm and M. Juliana McElrath of Fred Hutchinson Cancer Research Center; Lindsey Baden and Jennifer Johnson of Brigham and Women’s Hospital; Julia Hutter, Edith Swann of National Institute of Allergy and Infectious Diseases, National Institutes of Health; Etienne Karita of Project San Francisco, Rwanda-Zambia HIV Research Group; Hannah Kibuuka of Makerere University Walter Reed Project; Juliet Mpendo of Uganda Virus Research Institute; Nigel Garrett and Kathy Mngadi of Center for the AIDS Programme of Research in South Africa;  Kundai Chinyenze and Frances Priddy of the International AIDS Vaccine Initiative; Sorachai Nitayapan of the Royal Thai Army, Armed Forces Research Institute of Medical Sciences; Punnee Pittisuttuthum of the Vaccine Trail Center, Mahidol University; Stephan Bart of Optimal Research LLC; Thomas Campbell of University of Colorado; Robert Feldman of Miami Research Associates; Gregg Lucksinger of Tekton Research; and Caroline Borremans, Katleen Callewaert, Raphaele Roten, Ludo Lavreys and Steven Nijs of Janssen Infectious Diseases BV.

This study was funded by Janssen Vaccines & Prevention BV and the National Institutes of Health (OD024917, AI068618, AI078526, AI096040, AI124377, AI126603, AI128751, TR001102), the Ragon Institute of MGH, MIT and Harvard, and a cooperative agreement (W81XWH-07-2-0067) between the Henry M Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the US Department of Defense. Medical writing support was provided by Katie Holmes (Zoetic Science), and was funded by Janssen Pharmaceuticals. We thank the International AIDS Vaccine Initiative (IAVI) and the generous support of USAID and other donors; a full list of IAVI donors is available online.