Investigational Preventative HIV Vaccine Well-Tolerated, Elicited Antibody Responses in Early Clinical Trials

In Phase 1/2a study, HIV-1 antibody response observed in 100 percent of healthy volunteers.

---

• Mosaic-based vaccine includes characteristics from several common strains of HIV.
• In the APPROACH multi-site, randomized and controlled study of 393 healthy people in five countries, investigational vaccines were well-tolerated and elicited antibody responses in 100 percent of volunteers.

BOSTON – An investigational preventative HIV vaccine being developed by researchers at Beth Israel Deaconess Medical Center (BIDMC) in collaboration with Janssen Vaccines & Prevention B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, and others has cleared an important hurdle in human clinical trials. In a large Phase 1/2a clinical trial, the vaccine was both well-tolerated and triggered the desired antibody response in 100 percent of the healthy volunteers. The results were announced by Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC together with colleagues from Janssen at the 9th International AIDS Society Conference on HIV Science in Paris.

“The genetic diversity of HIV presents an unprecedented challenge for designing an effective vaccine,” said Barouch, who is also Professor of Medicine at Harvard Medical School. “A successful preventative vaccine for HIV will need to provide broad protection against a wide range of viral strains. The positive, early-stage results of our ‘mosaic-based’ vaccines suggest the potential to achieve this goal.”

The mosaic-based vaccine regimen contains a patchwork of genetic sequences found in several strains of HIV that are prevalent worldwide. These snippets of genetic information are delivered to the body embedded within a non-replicating human cold virus. Including sequences from various different strains of HIV is intended to provide broad protection from the many strains of the virus.

Representing an early stage of clinical development, the Phase 1/2a APPROACH study evaluated several mosaic-based vaccines for their safety, tolerability and the ability to elicit an immune response against strains of HIV-1 in uninfected adults. As part of the multi-site trial, researchers evaluated the experimental vaccines among 393 uninfected volunteers in the United States, Rwanda, Uganda, South Africa and Thailand. They also tested various vaccine regimens by giving them as a series of four shots at different dosages and/or at different intervals of time.

The double-blind, placebo-controlled randomized APPROACH study demonstrated that all vaccine regimens were well-tolerated, with local pain and headache being the most frequently reported adverse effects. Additionally, the APPROACH study showed that certain vaccine regimens stimulated stronger immune system responses than others. The most promising regimen triggered an antibody response in 100 percent of study participants.

With a death toll of more than one million people each year, HIV/AIDS remains among the deadliest of infectious diseases. While anti-retroviral therapies currently available offer people with HIV hope of a close-to-average life expectancy, the cost and complexity of the drug regime puts it out of reach for the majority of the 37 million people living with HIV worldwide. 

“Despite the benefits of lifesaving antiretroviral treatment, it is unlikely that drugs alone will end the HIV epidemic,” said Barouch. “History is on the side of vaccines.” 

The study is the result of a major collaboration by 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), with the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH); the International AIDS Vaccine Initiative; the HIV Vaccine Trials Network (HVTN), and Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson. 

This work has been funded by grants from the Bill & Melinda Gates Foundation; the Ragon Institute of Massachusetts General Hospital, MIT and Harvard; the National Institutes of Health (NIH) Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program grants AI066305, AI078526 and AI096040; NIH grants AI060354; AI078526; AI0080280; AI084794; AI095985; AI096040; AI102660; AI102691; OD011170; HHSN261200300001E.