Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune response to unrelated antigens.

The HIV-1 Tat protein is able to raise a humoral immune response in the absence of adjuvant. Here, we investigated whether this property can be transferred to unrelated antigens. We first observed that Tat self-adjuvanticity is a T cell-dependent phenomenon in which a Th2 profile predominates. Then, we showed that the determinant governing the property is located in the region 1-57 of Tat and that fragment Tat1-57 can make two unrelated model antigens immunogenic in the absence of adjuvant. We found a Th2 pattern of immune response for both antigens, suggesting that Tat1-57 mediates this response. Next, we showed that, although less efficient than Tat1-57, the Tat37-57 fragment suffices to transfer the adjuvant property to other antigens. We also observed that preservation of cysteine 37 is absolutely required for the transfer, suggesting the role of disulphide-mediated dimerization in the transfer of the adjuvant property. Our observations suggest that for various antigens, the use of Tat37-57 or Tat1-57 or Tat22-57C(22-34)A might represent an alternative to adjuvants in humans, thereby opening up new perspectives in vaccination.