Development of a single-shot subunit vaccine for HIV-1. 5. Programmable invivo autoboost and long lasting neutralizing response

The subunit vaccine for HIV-1, recombinant glycoprotein 120 (rgp120), was u sed as a model antigen to evaluate the potential for a pulsatile single imm unization Vaccine formulation consisting of poly(lactic-co-glycolic) acid ( PLGA) microspheres. We designed rgp120 PLGA microsphere formulations that p rovide a pulse of rgp120 at 1 to 6 months (depending on the polymer) after administration, mimicking another immunization. In these studies, the in vi tro pulse of rgp120 correlated well with the observed in vivo autoboost as measured by an increase in anti-gp120 antibodies in guinea pigs. The immune response to the rgp120 PLGA microsphere formulations was increased by addi ng the soluble form of the saponin-derived adjuvant, QS-21. The use of smal l microspheres, however, did not increase the humoral response to rgp120. A single immunization with rgp120 PLGA microspheres resuspended in soluble r gp120 and QS-21 elicited neutralizing antibody titers that were comparable to titers obtained from two immunizations of rgp120 and QS-21 at the same t otal dose. Administration of rgp120 PLGA microspheres in baboons resulted i n high, long-lasting neutralizing antibody titers that were greater than re peated immunizations with soluble rgp120 and QS-21. These studies also indi cated that a continuous release of QS-21 at the injection site may provide a greater immune response than a bolus injection. Overall, this work demons trated that PLGA microsphere formulations may be designed to provide in viv o pulses of an antigen eliminating the need for repeated immunizations.