Vaccine-elicited memory cytotoxic T lymphocytes
Attempts to create an effective and safe vaccine for the prevention of human immunodeficiency virus (HIV) infection and disease have so far proven unsuccessful. Since virus-specific cytotoxic T lymphocytes (CTL) contribute to the control of HIV/SIV replication, most vaccine approaches being pursued include strategies for stimulating T cell responses. To facilitate the rational development of vaccine strategies that will elicit such memory T cell populations, we need to understand the mechanisms contributing to the development of vaccine-elicited memory CTL. We here describe the kinetics of the virus-specific CD8 + T lymphocyte responses following immunization of mice with three different vaccine vectors encoding HIV-1 Envelope (Env): plasmid DNA, recombinant vaccinia virus (rVac), and recombinant adenovirus (rAd). We prospectively monitored levels of antigen-specific CD8+ T cells in the blood and spleens of these mice using tetramers and characterized the effector and memory CTL elicited by each of these vaccine vectors by measuring their cell-surface expression of a variety of activation- and maturation-associated molecules. We found that the kinetics of CTL generation differed with each different vaccine modality, and observed no correlation between the phenotypic characteristics of rVac-elicited Env-specific CD8+ memory T cells and their functional capacities. The immunogenicity and pathogenicity of novel rVac constructs were assessed as part of an effort to create novel, safe immunogenic vaccine vectors for use in human populations. Finally, we observed that interferon-gamma (IFNγ) plays a role in damping the development of effector and memory CD8+ T cell populations generated by rAd immunization. Attempts to rationally design HIV-1 vaccines remain confounded by limitations in our understanding of the mechanisms underlying memory T cell generation. With a better understanding of these processes, we will be able to better define interventions for improving their development.
0379: Cellular biology