Modulation of antigen-specific humoral responses in rhesus macaques by using cytokine cDNAs as DNA vaccine adjuvants

An important limitation of DNA immunization in nonhuman primates is the dif ficulty in generating high levels of antigen-specific antibody responses; s trategies to enhance the level of immune responses to DNA immunization may be important in the further development of this vaccine strategy for humans . We approached this issue by testing the ability of molecular adjuvants to enhance the levels of immune responses generated by multicomponent DNA vac cines in rhesus macaques. Rhesus macaques were coimmunized intra muscularly with expression plasmids bearing genes encoding Th1 (interleukin 2 [IL-2] and gamma interferon)- or Th2 (IL-4)-type cytokines and DNA vaccine constru cts encoding human immunodeficiency virus Env and Rev and simian immunodefi ciency virus Gag and Pol proteins. We observed that the cytokine gene adjuv ants (especially IL-2 and IL-4) significantly enhanced antigen-specific hum oral immune responses in the rhesus macaque model. These results support th e assumption that antigen-specific responses can be engineered to a higher and presumably more desirable level in rhesus macaques by genetic adjuvants .