Lessons learned from HIV-1 vaccine trials: new priorities and directions

Abstract

A vaccine against human immunodeficiency virus (HIV) seems to be on the horizon. Correlates of risk of infection for [corrected] the RV144 vaccine trial have been found. There is understanding of what makes HIV envelope-specific antibodies broadly neutralizing and new T cell vaccine approaches can overcome virus variability.

Figure 1

Three possible protective outcomes of an HIV-1 vaccine. The immune response to a vaccine (left) and possible outcomes after later exposure to HIV-1 (right). Top right, the antibody response after vaccination is strong and broad enough to neutralize the HIV-1 before infection can be established. Middle right, the immune responses, CD8⁺ T cells, non-neutralizing antibodies and/or natural killer cells (NK cells) that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) clear the infection within days of exposure. Bottom right, the infection is established, but the CD8⁺ T cell response, possibly aided by antibody and innate responses, establishes very good control of the virus with a very low virus load and prolonged survival (without the need for antiretroviral therapy). CTL, cytotoxic T lymphocyte; ADCVI, antibody-dependent cell-mediated viral inhibition.

A successful HIV vaccine will probably juggle broadly neutralizing antibodies with strong T cell responses to achieve efficacy.