A phase 2b clinical trial of a novel preventive HIV vaccine regimen developed by researchers at the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard, Beth Israel Deaconess Medical Center (BIDMC), and partners has begun in southern Africa. The investigational regimen is designed to induce responses to different strains of the virus found in many regions of the world. The new study is the first to test whether the vaccine is able to reduce the incidence of HIV infection.
"One of the major challenges for HIV vaccine development is the tremendous genetic diversity of the virus," explains Bruce Walker, MD, director of the Ragon Institute. "Viruses from patients in Boston may be 40 percent different from viruses found in Africa, so developing a vaccine that can protect against these diverse strains is an enormous, unprecedented challenge."
The vaccine regimen being tested, originally developed in the laboratory of Ragon Institute founding member Dan H. Barouch, MD, PhD, includes a mosaic vaccine, so called because it contains genetic sequences from different HIV strains prevalent in many parts of the world. "A safe and effective global HIV vaccine will almost certainly be needed to end the HIV epidemic," says Barouch, who is also director of the Center for Virology and Vaccine Research at BIDMC and a professor of Medicine at Harvard Medical School. "This clinical trial will determine whether this vaccine candidate will prevent HIV infection in young women in sub-Saharan Africa."
Barouch began pursuing the mosaic vaccine strategy in 2007, and early versions of mosaic vaccines tested in several animal models showed very promising results prior to initial human testing. Earlier this year, Barouch and partners reported preliminary results of the phase 1/2a APPROACH study at the 9th International AIDS Society Conference on HIV Science, indicating that the experimental vaccine appeared to be well tolerated and that the most promising regimens triggered the desired antibody responses in all of healthy volunteers who received them. The APPROACH trial was sponsored by the Janssen Pharmaceutical Companies of Johnson & Johnson with support from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, the Ragon Institute and other partners.
Walker, who is the Ragon Professor of Medicine at Harvard Medical School, explains that funding from the Ragon Institute was crucial to initial human trials of the mosaic vaccine. "This vaccine represents a remarkable example of how philanthropy can accelerate scientific advances. Bringing any vaccine from animal testing into human trials requires a major scientific effort as well as financial resources. A gift from Phillip T. (Terry) and Susan Ragon has been critical to the research and has helped to get this vaccine to the stage where it can be tested for efficacy." The initial gift from the Ragons established the Ragon Institute, and their continued support has enabled a number of advances against HIV and other infectious diseases.
"The Ragon Institute was established to harness the immune system to prevent and cure disease, with the initial goal of making an effective HIV vaccine" says Terry Ragon, who is founder, owner, and CEO of the software company InterSystems Corporation. "Our hope is that, in solving what is perhaps the most difficult and deadly of all infectious diseases, we'll find ourselves in the position of being able to cure a wide range of other diseases as well. "
Called the Imbokodo trial from the Zulu word for "rock" - echoing a South African proverb that refers to the strength of women and their importance in the community - the new study has begun enrolling young women in South Africa, the country with the greatest prevalence of HIV infection worldwide. Regulatory approval is being sought in Malawi, Mozambique, Zambia and Zimbabwe. The trial is being conducted at clinical sites coordinated by the HIV Vaccine Trials Network in collaboration with southern African scientists.
Imbokodo has a goal of enrolling 2,600 uninfected, sexually active women, ages 18-35, who will receive vaccinations at four timepoints over one year - either the experimental, mosaic-based vaccine regimen or a placebo - to determine whether the vaccine regimen can reduce the incidence of HIV infection. Additional information on the trial is available at ClinicalTrials.gov using identifier NCT03060629 and at http://www.
The Janssen Pharmaceutical Companies of Johnson & Johnson collaborated with Barouch on the development of the mosaic vaccine. The Imbokodo study is being sponsored by Janssen Vaccines & Prevention, B.V. - part of the Janssen Pharmaceutical Companies - with co-funding from two primary partners, the National Institute for Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation. Additional funding is being provided by the Ragon Institute, the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, and the U.S. Army Medical Materiel Development Activity.
The Ragon Institute of MGH, MIT and Harvard was established in 2009 with a gift from the Philip T. and Susan M. Ragon Foundation, creating a collaborative scientific mission among these institutions to harness the immune system to combat and cure human diseases. The primary initial focus of the institute is to contribute to the development of an effective AIDS vaccine. The Ragon Institute draws scientists and engineers from diverse backgrounds and areas of expertise across the Harvard and MIT communities and throughout the world, in order to apply the full arsenal of scientific knowledge to understanding mechanisms of immune control and immune failure and to apply these advances to directly benefit patients.