Each team is pursuing a unique vaccine strategy, and these strategies include DNA vaccines, virus vector vaccines, subunit vaccines and virus-like particle vaccines. None of the vaccines contain the genetic information to make a complete virus, and therefore they pose no threat of HIV infection to potential study participants.
"A safe and effective HIV vaccine is critical to the control of HIV globally," says Anthony S. Fauci, M.D., NIAID director. "These new awards will speed the development of promising HIV vaccine candidates that are based on recent advances in HIV vaccine design and on the latest discoveries in HIV virology and immunology."
The four research organizations that have received awards and summaries of their proposed projects follow.
AlphaVax Human Vaccines, Inc., Durham, North Carolina
Under the direction of Jeffrey D. Chulay, M.D., researchers at AlphaVax will use non-replicating alphavirus particles as a vector to deliver the genes to make four HIV proteins (gag, pol, env and nef). This novel vaccine induces strong cellular and antibody immune responses in animal models, including non-human primates. The genes in this vaccine have been taken from HIV strains in circulation in South Africa to maximize the probability that the vaccine would be successful in populations with the highest prevalence of HIV/AIDS.
This new work builds on experience AlphaVax has obtained from making and testing a similar "proof-of-concept" vaccine that contains only the HIV gag gene. Clinical testing of this early construct, funded through the NIAID-sponsored HIV Vaccine Trials Network and the South African AIDS Vaccine Initiative, is underway in the United States and is being planned for South Africa.
Epimmune, Inc., San Diego, California
Mark J. Newman, Ph.D., and colleagues at Epimmune, in collaboration with researchers at Bavarian-Nordic in Denmark, propose developing an epitope-based HIV vaccine to be given in a prime/boost regimen. Epitopes are the small pieces of a foreign protein to which immune system cells specifically attach and that enable them to recognize a pathogen as foreign. Epitope-based vaccination is a promising but as yet unproven technology that could be applied to many infectious diseases.
The priming inoculation will be a DNA-based vaccine expressing HIV epitopes specifically selected to induce immune responses in most of the world's population. The same HIV epitopes expressed in a modified vaccinia Ankara virus (MVA) vector will boost the priming DNA immunization. In non-human primates, MVA vector vaccines have already been shown to boost both cellular and antibody immune responses to DNA vaccinations.
This project will test the potential usefulness of epitope-based vaccines. It builds on the experience Epimmune is obtaining from ongoing clinical trials in the United States and Botswana of a "proof-of-concept" DNA vaccine containing only HIV epitopes specific to the cellular immune response.
Novavax, Inc., Columbia, Maryland
D. Craig Wright, M.D., Chief Scientific Officer of Novavax, Inc., and colleagues, including Robin A. Robinson, Ph. D., Director of the Vaccine Division and Principal Investigator, in collaboration with academic researchers at Emory University in Atlanta, GA, are developing and testing a novel virus-like particle (VLP) vaccine. The genes that encode the main structural proteins of HIV (the envelope and gag core proteins) will be expressed in insect or mammalian cells. These proteins self-assemble to form VLPs, and the resultant VLPs, devoid of the virus genes themselves, will be purified to form the vaccine. The investigators propose to deliver this protein-based vaccine in a manner that they predict will induce broad neutralizing antibodies in blood and mucosal tissues. The HIV genes for this vaccine have been taken from HIV strains in circulation in the United States.
Progenics Pharmaceuticals, Tarrytown, New York
Under the direction of Paul Maddon, M.D., Ph.D., researchers from Progenics Pharmaceuticals and the Weill Medical College of Cornell University in New York City will develop and test a modified HIV envelope subunit HIV vaccine. Progenics' collaborator at Cornell (John Moore, Ph.D.) will modify the structure of the HIV envelope protein to enhance its ability to generate broadly cross-reactive, neutralizing antibodies. Progenics will manufacture and then enhance these modified envelope proteins by pairing them with a vaccine adjuvant that will optimize their delivery. The groundwork based on HIV isolated in the United States will be applied to the development of a vaccine based on a subtype C envelope protein from a South African isolate, so that vaccine testing can move swiftly into developing country settings. This project will determine if the modifications to the virus envelope protein designed by the Progenics team can induce high levels of broadly reactive neutralizing antibodies against HIV, and, if successful, whether such antibodies protect against HIV infection and AIDS.
These vaccine development contracts are part of NIAID's expanded commitment to develop an HIV vaccine, and they complement other NIAID-supported HIV vaccine research and development activities. For more information on all HIV vaccine programs at NIAID, visit www.niaid.nih.gov/daids/vaccine.
NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.