HIV vaccines: can mucosal CD4 T cells be protected?
OBJECTIVE
The aim of this article is to understand the significance of protecting the mucosal tissue compartment during acute HIV infection, and to describe the current efforts towards this goal.


RESULTS
The mucosa is the primary route of HIV transmission, and serves as a major site for viral dissemination leading to a massive destruction of the memory CD4 T cell compartment. This destruction is mediated as a consequence of direct viral infection and occurs in all the tissues of the body suggesting that once infection explodes out of the mucosal tissues memory CD4 T cells at all other sites are very rapidly infected and destroyed.


CONCLUSIONS
The enrichment of highly susceptible CD4 targets in mucosal tissues suggests that the immune system will need to be in a state of high alert to contain infection once HIV crosses the mucosal barrier. This will require the generation and maintenance of strong vaccine-induced neutralizing antibodies and CD8 T cell responses in mucosal tissues. Given the challenges of inducing neutralizing antibodies, current efforts are focused on developing a T cell based vaccine that can contain the spread of HIV infection. Developing a T cell based vaccine is hampered by the lack of any predictive correlates of protection. In the absence of such correlates, protection can be measured by the extent to which mucosal CD4 T cells are preserved. Preservation of mucosal CD4 T cells will have a significant impact on disease course and long-term outcome.
Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20895, USA. jmattapallil@mail.nih.gov
Joseph J
JJ
Mattapallil
Mario
M
Roederer