Mucosal Vaccination Against HIV-1

Abstract

Sexual mucosal transmission of HIV-1 is the most common means of spread of HIV/AIDS throughout the world. Although it may be reasonable to assume that a vaccine that works to eliminate viral replication in the systemic lymphoid tissue may be partially protective, there is still a reasonable belief that a vaccine that engenders high level of immune defenses at mucosal surfaces will be needed in the quest for an effective HIV immunization regimen. Despite some positive advances, the fact remains that no candidate vaccine to date has elicited antibodies which can broadly neutralize a wide variety of primary HIV-1 virus isolates in humans. Moreover, the benefit of inducing either a quantitatively or qualitatively different response at the mucosal level has not been adequately addressed experimentally. Unfortunately, many of the same concerns are valid for the vaccines which have been developed to induce cytotoxic T cell responses to HIV, in an attempt to control HIV-1 replication in infected cells. Thus, all studies to date must be interpreted in the context of the failure of all human trials of HIV vaccines to date, and a lack of known correlates of immunity pending such a vaccine success.

This chapter thus focuses on non-human primate and human investigations of mucosal immunization for HIV-1. the pre-clinical evidence that mucosal routes of vaccination, or even mucosal induction of immune responses using systemic vaccination, provide complete or partial protection from HIV-1 infection or disease is evolving. Although most of the animal studies, especially in the macaque model, would imply that vaccination via the nose, rectum or vagina may be needed for optimum vaginal or rectal responses, that data is still weak and not substantiated by any human clinical trial. It is clear that we still do not know the optimum route, the desired antibody response, the qualitative or quantitative nature of the T cells and their homing markers that need to be induced, or the specific approach that will allow for development of an effective mucosal HIV vaccine. Indeed, there is still debate as to whether neutralizing antibodies or CTL or yet undefined immune parameters, either in mucosal or systemic compartments or both, may correlate with protection against infection or disease. Nonetheless, most investigators in the HIV-1 vaccine field believe that mucosal responses will be needed and may be central to eventual success.