Liposome-Encapsulated HIV-1 gp120 Induces Potent V1V2-Specific Antibodies in Humans.

Background: In the RV144 trial, HIV-1 gp120 V1V2 antibodies correlated inversely with risk of HIV-1 infection; however the titers waned quickly. We hypothesized that a more potent adjuvant might enhance the magnitude and durability of V1V2 antibodies.

Methods: We examined archived sera from a phase I randomized, double blind placebo-controlled trial, conducted in HIV-1 uninfected individuals, vaccinated with HIV-1SF-2 rgp120 either adsorbed to aluminum hydroxide (aluminum hydroxide arm) or encapsulated in liposomes containing monophosphoryl lipid A (MPL®) and then adsorbed to aluminum hydroxide (liposomal arm).

Results: The median IgG antibody titers across weeks 10-112 were higher in the liposomal arm against subtypes B (2-16-fold), AE (4-8-fold) and C (4-16-fold) V1V2 proteins. High titers were maintained even at 10 months post last boost in the liposomal compared to the aluminum hydroxide arm. The antibodies exhibited ADCC and 47-integrin receptor inhibition-binding functions.

Conclusion: Inclusion of two adjuvants in the vaccine formulation, aluminum hydroxide and liposomal MPL®, induced robust, durable, and functional antibodies. Based on the magnitude of antibody responses and the percentage of coiled and -sheet in the predicted V2/V3-peptide structure, we speculate that liposomal gp120 was presented in a conformation that favored the induction of robust antibody responses.

Trial Registration: ClinicalTrials.gov # NCT00001042.