Wilson Vaccine Discovery Consortium

OVERVIEW:

The existence of adenovirus-specific central memory CD4 T cells in human blood provides a setting whereby vaccination with an adenoviral vector could quickly expand a population of potential HIV target cells whose migration to the gut may be facilitated by persistent gut-associated antigen. The Wilson-led VDC’s research focuses on clarifying the biology of adenovirus vaccines in the context of their application to HIV which should help the field proceed with the development of second generation vaccines in a rational, expedient, and safe manner.

The first major goal of the VDC is to undertake an epidemiologic assessment of adenovirus infections in men who have sex with men. A total of 100 HIV negative gay men, half of whom are seropositive with respect to anti-adenovirus antibodies and half seronegative, will be enrolled in a study in which the research team will measure neutralizing antibodies titers and T cells to adenoviruses from peripheral blood. A sigmoidoscopy will be performed to harvest rectal washings for isolation of adenoviruses and mucosal biopsies will be performed for characterization of adenovirus-specific T cells that may be gut-associated (GALT). These studies will progress through the 3 years of the grant. The deliverable will be an epidemiology data set in the context of these cohorts and will include a statistical analysis with respect to the correlations if any with anal-receptive sexual intercourse. These studies will provide critical information regarding the biology of adenovirus infections in populations who are candidates for future HIV vaccine studies.

The second major goal of the research project is to characterize natural adenovirus infections in macaques. This will form the foundation for the development of an animal model for studying vaccine-induced enhanced acquisition of SIV. One way to accomplish this is to develop a vaccine from a macaque-derived adenovirus that when used in macaques simulates the kind of host-vector interactions one would see with HAdV5 vectors in humans. The actual use of this vaccine in macaques for studying efficacy and/or increased susceptibility to SIV infection falls beyond the scope of this grant and will be done in collaboration with a primate center.