T cell Mosaic Vaccine
Overcoming HIV diversity is a prime goal of an HIV vaccine. The Center for HIV/AIDS Vaccine Immunology (CHAVI) and now the Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) have developed a mosaic vaccine that is designed in silico and optimizes the coverage of T cell immune responses to globally diverse HIV strains. The T cell mosaic vaccine was developed by Dr. Bette Korber at Los Alamos National Laboratory within the Duke CHAVI-ID and is being tested for the first time in a human clinical trial. This trial is being conducted by the HIV Vaccine Trials Network, and Dr. Lindsey Baden of Harvard University is the Clinical Trial Principal Investigator. The clinical sites for the trial include Harvard University, the University of Rochester, the University of Alabama, and Basel Switzerland. The vaccine was produced from joint funding from the Division of AIDS, the National Institute of Allergy and Infectious Diseases (NIAID), the National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation.
Sequential Vaccine of Evolved Envelope Mutants
Inducing broad neutralizing antibodies (BnAbs) is a prime goal of HIV vaccine development. However, the work of the Duke CHAVI-ID team has demonstrated that host tolerance control factors either directly or indirectly limit BnAb induction and make BnAb clonal lineages disfavored or subdominant in immune responses. To overcome this limitation, the Duke CHAVI-ID team has studied multiple individuals with BnAbs from the time of transmission to BnAb induction and has begun to develop immunization regimens that are based on the envelope proteins that induce BnAbs in vivo. The first such vaccine, the CH505 vaccine, has now been funded by the Division of AIDS, the NIAID, and the NIH. This vaccine is currently being produced according to good manufacturing practices (GMP) by KBI Pharmacia, Inc. of Durham, North Carolina. Clinical trials are currently being designed by the HIV Vaccine Trials Network and are targeted to begin in early 2015. The Duke CHAVI-ID has received support from the Division of AIDS, the NIAID, and the NIH for the GMP production of Envs for this trial.
HIV Env Gp41-Liposomal Vaccine for Neutralizing Antibody Induction
This vaccine will utilize an immunogen that is designed to mimic a viral particle. Neutralizing determinants for the gp41 membrane proximal external region are exposed on the surface of the artificial particle. This immunogen has the property of binding to HIV env gp41 broad neutralizing antibodies but not binding to gp41 non-neutralizing antibodies. In partnership with the Infectious Disease Research Institute in Seattle, Washington, Duke has recently received a grant from the Bill and Melinda Gates Foundation for the GMP production of this immunogen for human clinical trials.