Probing the possibilities for T-cell-based AIDS vaccines

Abstract

This review will discuss the current challenges facing the development of a successful AIDS vaccine and approaches being pursued to overcome them, with an emphasis on vaccines designed to elicit primarily cellular, rather than humoral, antiviral immune responses. Recent insights into the biology of mucosal virus transmission, CD4 T-cell depletion dynamics, the character of virus-specific CD8 T-cell responses, and the dynamic effects that CD8 T cells exert on virus evolution and genetic diversity manifest during lentivirus infections have engendered an improved understanding of the anatomical, physiological, and immunological aspects of HIV infection. These advances help frame the key scientific hurdles to development of a safe and effective AIDS vaccine that an expanding number and diversity of experimental approaches in vaccine design, administration, and evaluation are now seeking to overcome. The development of an effective AIDS vaccine remains elusive. Our increasing knowledge regarding the biology of HIV infection, mechanisms of AIDS pathogenesis, and correlates of protective immunity, however, suggest new hypotheses which, when critically evaluated, should bring us closer to the realization of an AIDS vaccine - or at least an improved understanding of the true nature and magnitude of the obstacles ahead.