DEVELOPMENT OF A SINGLE-SHOT SUBUNIT VACCINE FOR HIV-1 .2. DEFINING OPTIMAL AUTOBOOST CHARACTERISTICS TO MAXIMIZE THE HUMORAL IMMUNE-RESPONSE

The design of a single-shot subunit vaccine for HIV-1 with polylactic- coglycolic acid (PLGA) sustained-release technology to effect an autob oost of antigen (MN gp120) at a given time after the primary immunizat ion requires in-depth knowledge about the timing, the duration, and th e need for coadjuvant in the autoboost. These questions cannot be answ ered unambiguously with PLGA microspheres, so we have conducted studie s using Alzet minipumps to release antigen at prescribed times to mimi c a PLGA autoboost. The results show that a discrete autoboost is pref erred over continuous release of antigen, that the time profile of the autoboost (whether pulsatile or a 2-week continuous release) does not affect the booster immune response, and that only antigen is required in the booster immunization (a coadjuvant in the boost does not give higher titers).