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-VLPAs), 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.
ASJC Scopus subject areas
- Infectious Diseases