Perpetuation of vaccine memory T cell responses against SIV/HIV

Abstract

Results of the RV144 study of a prime‐boost regimen combining a canarypox vector‐based candidate ALVAC‐HIV (vCP1521) and AIDSVAX B/E gp120 human immunodeficiency virus (HIV) envelope showed a modest but statistically significant 31% reduction in the rate of HIV infection in healthy volunteers (Rerks‐Ngarm et al, 2009). These promising results need to be confirmed in further clinical trials and researchers are hoping to gain more information about the correlates of protection against HIV and the mechanisms of action of these vaccines. In addition, from a clinical standpoint, the RV144 study provides two interesting pieces of information. First, at the end of the first year of the study the rate of protection was up to 60% in vaccinees compared to placebo recipients. Second, no differences in terms of peak of viral load were seen between vaccinated and placebo recipients who became infected. This suggests that the protective efficacy wanes overtime and that vaccines were unable to control viral replication once a systemic infection is established. The immune system controls pathogens through the generation of memory T cells, which can be divided in, at least, two populations of central and effector memory T cells (Tcm and Tem) ensuring protection for years after the first encounter of the pathogen. Following antigen exposure, Tcm undergone expansion, differentiation towards effector cells, which patrol mucosal tissues, the site of entry of HIV and kill infected cells. Clearly, the initial hours following exposure of HIV to mucosal tissues represents a window of opportunity for the immune system to control and/or to eliminate smaller and localized foci of HIV‐infected cells. Therefore, an effective vaccine must confer to the host the capability to win the race between the differentiation capacity of Tcm and the extraordinary burst of HIV replication, which occurs within hours before the establishment of an irreversible disseminated …