DEVELOPMENT OF A SINGLE-SHOT SUBUNIT VACCINE FOR HIV-1

The successful development of an AIDS vaccine will require formulation s that not only invoke the desired immunological response, but also ar e stable and easy to administer. A single shot MN rgp120 vaccine formu lation comprised of MN rgp120 encapsulated in poly (lactic-coglycolic) acid (PLGA) microspheres was developed to provide an in vivo autoboos t of antigen. These formulations were designed to yield an in vivo aut oboost at 1, 2, 3 or 4-6 months. In addition, PLGA microspheres contai ning the adjuvant, QS21, were also prepared to provide an in vivo auto boost concomitant with antigen. In guinea pigs, these formulations yie lded higher anti-MN rgp120 and anti-V3 loop antibody titers than alum formulations that were administered at higher antigen doses. Different doses of encapsulated MN rgp120 provided a clear and well-defined dos e response curve for both anti-MN rgp120 and anti-V3 loop antibody tit ers. When soluble QS21 was mixed with the encapsulated MN rgp120, the antibody titers were increased by a factor of 5 over the titers with e ncapsulated MN rgp120 alone. An additional fivefold increase in antibo dy titers was observed for guinea pigs immunized with encapsulated MN rgp120 and QS21 on the same microspheres. These results suggest that t he adjuvant properties of QS21 can be increased by microencapsulation in PLGA. Furthermore, antibodies induced by these preparations neutral ized the MN strain of HIV-1. The neutralization liters for sera from a nimals immunized with MN rgp120-PLGA and soluble QS21 were greater tha n the titers obtained from guinea pigs that were treated with MN rgp12 0 and soluble QS21 at the same dose. Overall, these studies validate t he in vivo autoboost concept, reveal a method for improving the adjuva nt properties of QS21, and indicate the potential of future single sho t vaccine formulations.