Lymphoid activation: a confounding factor in AIDS vaccine development?

In a previous vaccination trial, inoculation of env gene DNA failed to elicit a detectable antibody response, yet accelerated virus dissemination in most immunized cats following challenge with feline immunodeficiency virus. This result raised the possibility that cell-mediated immune responses had given rise to immune-mediated enhancement of infection. Since high-level replication of immunodeficiency viruses in lymphocytes requires cellular activation, antigen-specific responses or non-specific polyclonal activation may have increased the frequency of optimal target cells. In the present DNA vaccination trial, although designed so as to minimize non-specific polyclonal activation, immune-mediated enhancement was nonetheless observed in certain immunized cats. Moreover, rapid virus dissemination in vivo was associated with the presence of T-helper responses prior to challenge, and was linked to increased susceptibility of lymphocytes to ex vivo infection. Immune activation may thus be a confounding factor in vaccination against lentivirus infection, diminishing vaccine efficacy and giving rise to immune-mediated enhancement.