HIV vaccines: can CD4+ T cells be of help?

Defining immune correlates of protection against the human immunodeficiency virus (HIV) remains a major challenge. While the role of neutralizing antibodies and CD8+ T cell responses has been widely acknowledged and applied in vaccine development, little vaccine candidates have focused on CD4+ T cells. As the main target of HIV, CD4+ T cells play a pivotal role in HIV infection. An HIV vaccine that elicits strong, multi-specific, polyfunctional and persisting CD4+ T cell responses would therefore have the potential of lowering viral set point when HIV infection occurs or reducing viral load in already infected patients. In a combined approach with neutralizing antibodies and CD8+ T cells, CD4+ T cells cannot only enhance the magnitude, quality and durability of the desired antibody response, but will also provide the help needed to induce and maintain effective antiviral CD8+ T cell responses. In addition, the disease-modifying potential of the CD4+ T cell response, by lowering viral set point and/or viral load and thus probability of transmission, may be beneficial both at the individual and public health level.