Understanding the mechanisms and limitations of immune control of HIV

Abstract

A large number of experimental studies have been performed over the past decade in an attempt to develop a vaccine for human immunodeficiency virus (HIV). These studies have used a variety of approaches aimed at stimulating both antibody-mediated and cell-mediated immunity. Many of these experiments have been performed in macaque models of HIV. Analysis and modeling of the results of these studies provide the opportunity to investigate the mechanisms and limitations of viral control by humoral and cell-mediated immunity. These studies suggest that CD8+ T cells do ‘too little too late’ to prevent the establishment of viral infection and latency. By contrast, passively administered antibody acts extremely early to reduce the initial inoculum and slow viral growth. In both cases, reduction in peak viral load appears crucial to the maintenance of CD4+ T cells in acute infection and for effective long-term viral control. The insights gained from studies of simian human immunodeficiency virus infection have important implications for HIV vaccination. However, important questions remain as to whether differences in pathogenesis in HIV will lead to different ‘rules of engagement’ for immune control of virus.