DURHAM, N.C. - Duke University Medical Center vaccine experts have assembled an international team of investigators to design and implement the first human trial of a mosaic HIV vaccine candidate, a novel strategy that attempts to counter one of the most daunting challenges in HIV vaccine design: the virus's extensive genetic diversity.
Traditional HIV vaccines are designed to stimulate the body's immune system to recognize naturally occurring stretches of specific amino acids in the virus's proteins. In contrast, mosaic vaccines are composed of many sets of synthetic, computer-generated sequences of proteins that can prompt the immune system to respond to a wide variety of circulating HIV strains.
Such vaccines have already been studied in animals and have shown some success in enhancing the breadth of immune responses. Now, Barton Haynes, MD, director of the Duke Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology (CHAVI), says a newly formed research coalition has begun designing an early phase safety trial to assess mosaic vaccines in humans. The trial will test the mosaic concept and could possibly lead to the next generation of HIV vaccine candidates.
Haynes, who will lead the consortium, says the group will use the NYVAC vaccinia vector (derived from the vaccine to protect against smallpox) and DNA that contain a new set of artificial computer-designed HIV genes in a phase I clinical trial that will be supported by the Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Haynes says the consortium hopes to launch human trials by late 2012.
The consortium includes many of the world's leading researchers and organizations committed to finding an effective vaccine to protect against HIV infection, including
The Foundation for the National Institutes of Health, the Fred Hutchinson Cancer Research Center and its NIH-funded HIV Vaccine Trials Network, the IPPOX Foundation in Switzerland, Beth Israel Deaconess Medical Center, Los Alamos National Laboratory, the NIH/NIAID Vaccine Research Center, Duke University and its Center of HIV/AIDS Vaccine Immunology, the Bill & Melinda Gates Foundation and the Division of AIDS of the National Institute of Allergy and Infectious Diseases.
Bette Korber, a senior scientist at Los Alamos National Laboratory and leader of the team that developed the mosaic genes, noted "HIV's diversity is vast, and the mosaic gene design represents a novel vaccine design to directly tackle HIV diversity in human clinical trials. Based on computational models, mosaic vaccines were predicted to perform better than natural HIV genes; experimental studies in animals that directly compared mosaic to natural vaccines supported that prediction. We are excited to test this concept in humans."
"Each member of this consortium is also a member of the Global HIV Vaccine Enterprise, and this collaboration is truly a global effort to make progress on HIV vaccine development," said Haynes.
The NYVAC vaccine is being provided by Sanofi-Pasteur, which is a collaborator in the study. The clinical development of NYVAC HIV vaccines has to date been conducted in Europe primarily through the EuroVacc Program.