Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Development of a single-shot subunit vaccine for HIV-1.
AIDS Res Hum Retroviruses. 1994;10 Suppl 2:S21-6. Unique Identifier : AIDSLINE MED/95169484 Cleland JL; Powell MF; Lim A; Barron L; Berman PW; Eastman DJ; Nunberg JH; Wrin T; Vennari JC; Department of Pharmaceutical Research and Development, Genentech,; Inc., South San Francisco, California 94080.
Abstract:
The successful development of an AIDS vaccine will require formulations that not only invoke the desired immunological response, but also are stable and easy to administer. A single shot MN rgp120 vaccine formulation comprised of MN rgp120 encapsulated in poly (lactic-coglycolic) acid (PLGA) microspheres was developed to provide an in vivo autoboost of antigen. These formulations were designed to yield an in vivo autoboost at 1, 2, 3 or 4-6 months. In addition, PLGA microspheres containing the adjuvant, QS21, were also prepared to provide an in vivo autoboost concomitant with antigen. In guinea pigs, these formulations yielded 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 dose response curve for both anti-MN rgp120 and anti-V3 loop antibody titers. When soluble QS21 was mixed with the encapsulated MN rgp120, the antibody titers were increased by a factor of 5 over the titers with encapsulated MN rgp120 alone. An additional fivefold increase in antibody titers was observed for guinea pigs immunized with encapsulated MN rgp120 and QS21 on the same microspheres. These results suggest that the adjuvant properties of QS21 can be increased by microencapsulation in PLGA. Furthermore, antibodies induced by these preparations neutralized the MN strain of HIV-1. The neutralization titers for sera from animals immunized with MN rgp120-PLGA and soluble QS21 were greater than the titers obtained from guinea pigs that were treated with MN rgp120 and soluble QS21 at the same dose. Overall, these studies validate the in vivo autoboost concept, reveal a method for improving the adjuvant properties of QS21, and indicate the potential of future single shot vaccine formulations.
Keywords: Adjuvants, Immunologic/ADMINISTRATION & DOSAGE Alum Compounds/ADMINISTRATION & DOSAGE Animal AIDS Vaccines/ADMINISTRATION & DOSAGE/*ISOLATION & PURIF Comparative Study Delayed-Action Preparations Guinea Pigs Human HIV Antibodies/BIOSYNTHESIS HIV Envelope Protein gp120/ADMINISTRATION & DOSAGE/IMMUNOLOGY/ ISOLATION & PURIF HIV-1/*IMMUNOLOGY Microspheres Neutralization Tests Peptide Fragments/IMMUNOLOGY Polymers/ADMINISTRATION & DOSAGE Saponins/ADMINISTRATION & DOSAGE Vaccines, Synthetic/ADMINISTRATION & DOSAGE/ISOLATION & PURIF JOURNAL ARTICLE 950630
M9561132
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
