The Early Career Investigator (ECI) Scholar Award: Pilot Studies to Advance Non-Human Primate Models in Support of HIV Vaccine Clinical Research in FY2010
In 2010 four young investigators received the ECI award through the HVTN-CHAVI collaborative funding initiative. They are:
- Mohammed Asmal, Beth Israel Deaconess Medical Center of Harvard University
Novel transmitted Env SHIV for investigating mucosal transmission in macaques
To predict the success of HIV vaccines in humans, candidate vaccines are tested in macaques and challenged with SIV. However, often these challenge SIV viruses do not mimic the transmission event and course of the disease in humans. This project will generate novel chimeric HIV-SIV viruses incorporating the envelope of a virus that initiated an HIV-1 infection directly isolated from an acutely HIV-infected individual, and test the mucosal infectivity and immunogeniticity of these viruses in rhesus macaques. In the future, these novel chimeric viruses will be used for evaluating HIV candidate vaccines in macaques.
- Katharine Bar, University of Alabama at Birmingham
Neutralization sensitivity of SIVsm660 transmitted/founder viruses
SIVsmE660 is a commonly used challenge virus stock in rhesus macaque vaccine studies. However, the virus infection produces an inconsistent disease course in the monkeys following low-dose infection. This is believed to be because the stock contains viruses with a wide range of sensitivity to neutralizing antibodies as well as wide variation in replication ability. This proposal aims to identify specific SIVsmE660 virus clones of intermediate neutralization sensitivity that produce a consistent disease course, thereby improving the interpretability of the monkey model for evaluating candidate HIV vaccines.
- Anne-Sophie Dugast, The Ragon Institute of Massachusetts General Hospital
Impact of non-neutralizing antibodies on SHIV challenge
The results from the RV144 vaccine trial suggest that antiviral properties of non-neutralizing antibodies may be responsible for the modest protection against HIV infection. This project aims to isolate non-neutralizing antibodies that mediate antibody-mediated cellular cytotoxicity and complement mediated cytotoxicity activities from elite controllers, and determine whether these antibodies can provide protection from SHIV challenge in macaques.
- James Kobie, University of Rochester
Understanding the B cell response to SIV/HIV in non-human primates
The goal of an effective vaccine is to generate protective antibodies against the incoming pathogen. This investigator hypothesizes that, upon infection, the HIV virus subverts an effective antibody response by not only antigenic variation but also by promoting the development of suppressive antibody-producing cell types. This project proposes to examine the B cell response, and its role in a protective immune response against chimeric HIV-SIV virus infection in macaques. The results of this study will contribute significantly to understanding how such antibodies might be induced by preventive HIV vaccines.