Abstract

We have recently shown that HIV-1 Pr55gag virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLP(A)s), induce maturation and activation of antigen-presenting cells (APCs) in fresh peripheral blood mononuclear cells (PBMCs) from seronegative as well as seropositive, with either low or high viremia, HIV-1 subjects. A Th2 polarization has been observed in both HIV seropositive groups, which is efficiently boosted by HIV-VLP induction and does not switch into a Th1 pattern. Here we show that the production of the known immune-suppressive IL-10 is induced in both HIV-seropositive groups at a significantly lower level by HIV-VLPs compared to LPS. These levels, however, appear to still negatively interfere with the innate as well as adaptive Th1-polarized response observed in HIV-seropositive groups. These results indicate that vaccines and novel adjuvants (i.e., TLR agonists, such as LPS) must be evaluated not only for their immunogenicity but also for their potential immune-suppressive effects. In this perspective, fresh ex vivo PBMCs can be of high value for screening the responses as well as eventual failures of vaccinees enrolled in clinical trials.