BOSTON – A new study led by scientists at Beth Israel Deaconess Medical Center (BIDMC) demonstrates that a heterologous prime-boost HIV-1 vaccine regimen protected 50 percent of vaccinated non-human primates (NHPs) against challenges with the simian immunodeficiency virus (SIV), a virus similar to HIV that infects NHPs. Published today in the online edition of Science, these findings provide a new strategy for the clinical development of this novel HIV-1 vaccine candidate.
“Despite the urgent need for a safe and effective global HIV-1 vaccine, only four vaccine concepts have been evaluated for protective efficacy in humans over the past 30 years,” said lead author Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC and Professor of Medicine at Harvard Medical School. “We are very encouraged by the results of this latest preclinical HIV-1 vaccine study and believe the findings may lead to a clear path forward for evaluating this HIV vaccine candidate in humans.”
In this work, NHPs were first given a dose of adenovirus serotype 26 vectored vaccine to “prime” the immune system to mount an antibody response and then received a “boost” with a purified HIV envelope protein (the surface protein of the HIV virus), which enhances the immune system over time. (Adenovirus 26 is responsible for the common cold, and is engineered to serve as a carrier, or vector, to deliver pieces of SIV into cells.)
The study results showed that the prime-boost vaccine regimen provided complete protection in half of the vaccinated NHPs against a series of six repeated challenges with the simian immunodeficiency virus.
“Our previous studies of viral vector-based HIV-1 vaccine candidates showed much lower levels of protection against SIV,” said Barouch. “These new findings show that the envelope protein boost following the viral vector priming increases the magnitude and functionality of antibody responses and improves protection.”
Based on these pre-clinical data, the HIV-1 version of this vaccine regimen is now being evaluated in an ongoing Phase 1/2a international clinical study sponsored by Crucell Holland B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
More than 35 million people worldwide are infected with HIV and more than 2 million new infections develop each year. “Although antiretroviral therapies have prolonged the lives of HIV-1 infected patients, the definitive solution to this epidemic will likely be a vaccine,” said Barouch. “These new findings represent an important step forward.”
Barouch is a steering committee member of the Ragon Institute of MGH, MIT and Harvard.
The study was supported by the following grants from the National Institutes of Health: AI060354; AI078526; AI0080280; AI084794; AI095985; AI096040; AI102660; AI102691; OD011170; HHSN261200300001E, as well as funding from the Bill & Melinda Gates Foundation, and the Ragon Institute.
In addition to Barouch and Schuitemaker, coauthors include BIDMC investigators Erica N. Borducchi, Kaitlin M. Smith, Joseph P. Nkolola, Jinyan Liu, Jennifer Shields, Lily Parenteau, James B. Whitney, Peter Abbink, David M. Ng’ang’a, Michael S. Seaman, Christy L. Lavine, and James R. Perry; Galit Alter, Thomas Broge, and Caitlyn Linde of the Ragon Institute of MGH, MIT and Harvard; Margaret E. Ackerman and Eric P. Brown of the Thayer School of Engineering at Dartmouth; Wenjun Li of the University of Massachusetts Medical School; Arnaud D. Colantonio of the New England Primate Research Center; Mark G. Lewis of Bioqual; Bing Chen, of Boston Children’s Hospital; Holger Wenschuh and Ulf Reimer of JPT Peptide Technologies GmbH; Michael Piatak and Jeffrey D. Lifson of the AIDS and Cancer Program, Leidos Biomedical Research, Frederick National Laboratory; Scott A. Handley, and Herbert W. Virgin of Washington University School of Medicine; Marguerite Koutsoukos, Clarisse Lorin, and Gerald Voss of GSK Vaccines; and Mo Weijtens and Maria G. Pau of Janssen.
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.
BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and The Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.