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Microparticles in MF59, a potent adjuvant combination for a recombinant protein vaccine against HIV-1
D T O'Hagan1, M Ugozzoli, J Barackman
1Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA. derek_ohagan@cc.chiron.com
Abstract:
Novel adjuvant formulations involving PLG microparticles with entrapped recombinant protein antigens (env gp120 and p24 gag) from human immunodeficiency virus type-1 (HIV-1), dispersed in the emulsion adjuvant MF59 were evaluated as potential HIV-1 vaccine candidates in mice and baboons. In mice, the adjuvant combination induced significantly enhanced antibody responses in comparison to either adjuvant used alone. In addition, the polylactide co-glycolide polymer (PLG) microparticles and MF59 combination induced CTL activity against HIV-1 p24 gag. In baboons, the adjuvant combination induced significantly enhanced antibody titers after a single dose of gp120, but the responses were comparable to gp120 in MF59 alone after boosting. Both MF59+gp120 alone and PLG/gp120 in MF59 induced neutralizing antibodies against a T cell line-adapted (TCLA) strain and a primary isolate of HIV-1. In contrast to the observations with gp120, immunization in baboons with PLG/p24 in MF59 induced significantly enhanced antibody responses after boosting, in comparison to immunization with MF59 alone + p24.
Insights
Novel adjuvant formulations combining polylactide co-glycolide (PLG) microparticles and MF59 emulsion enhanced immune responses against HIV-1 antigens in animal models. This combination showed promise for developing effective human immunodeficiency virus type-1 (HIV-1) vaccines.
Area of Science:
- Immunology
- Vaccinology
- Biotechnology
Background:
- Developing effective human immunodeficiency virus type-1 (HIV-1) vaccines remains a global health priority.
- Adjuvants play a crucial role in enhancing vaccine immunogenicity and efficacy.
- Novel delivery systems are needed to improve antigen presentation and immune stimulation.
Purpose of the Study:
- To evaluate novel adjuvant formulations for HIV-1 vaccine candidates.
- To assess the immunogenicity of recombinant HIV-1 antigens (gp120 and p24 gag) encapsulated in polylactide co-glycolide (PLG) microparticles and dispersed in MF59 emulsion.
- To compare the immune responses induced by the novel formulations against existing adjuvant strategies in mice and baboons.
Main Methods:
- Recombinant HIV-1 env gp120 and p24 gag antigens were encapsulated in PLG microparticles.
- These microparticles were dispersed in the MF59 emulsion adjuvant.
- The formulations were administered to mice and baboons, and immune responses (antibody titers, CTL activity, neutralizing antibodies) were measured.
Main Results:
- In mice, the PLG microparticle and MF59 combination significantly enhanced antibody responses compared to individual adjuvants and induced CTL activity against HIV-1 p24 gag.
- In baboons, the combination induced enhanced antibody titers against gp120 after a single dose and against p24 after boosting, compared to MF59 alone.
- Both formulations induced neutralizing antibodies against T cell line-adapted and primary HIV-1 strains.
Conclusions:
- The novel adjuvant formulation combining PLG microparticles with MF59 emulsion demonstrates significant potential for enhancing immune responses against HIV-1 antigens.
- This formulation strategy warrants further investigation as a promising candidate for HIV-1 vaccine development.
- The findings suggest that combining particulate antigen delivery with emulsion-based adjuvants can effectively boost both humoral and cellular immunity against HIV-1.