Enhancing functional antibody responses against HIV envelope V1V2 through vaccine formulations

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Developing an effective HIV vaccine remains a significant global health challenge.
• Antibodies targeting the V1V2 domain of the HIV envelope glycoprotein are linked to reduced infection risk.
• These antibodies mediate Fc-dependent effector functions rather than potent neutralization.

Purpose of the Study:

• To evaluate V1V2-scaffold vaccines with various formulations for their ability to generate Fc-mediated antibody functions.
• To compare the immunogenicity and functional capacity of different adjuvant systems including lipid nanoparticles (LNPs).

Main Methods:

• BALB/c mice were immunized with V1V2-scaffold proteins using adjuvants like Addavax, IMDQ-PC/IVT, NE/IVT, and eLNP.
• Comparative groups included a V1V2-scaffold mRNA-LNP vaccine and an Env gp140 protein with MPLA/DDA adjuvant.
• Antibody responses were assessed for Fc-mediated activities such as antibody-dependent cellular phagocytosis and FcγRIV binding.

Main Results:

• V1V2-scaffold immunogens formulated with LNPs (eLNP and mRNA-LNP) induced the most robust and cross-reactive serum IgG responses.
• eLNP, mRNA-LNP, and IMDQ-PC/IVT formulations elicited functional IgG2a responses and Fc-mediated activities.
• Different formulations resulted in distinct IgG subclass profiles (IgG1 vs. IgG2a), with mRNA-LNP showing balanced responses.

Conclusions:

• Novel formulations, especially those utilizing lipid nanoparticles (LNPs), are effective in inducing functional V1V2-specific antibodies.
• These findings offer insights into optimizing HIV vaccine strategies by enhancing Fc-mediated effector functions.
• The study supports the development of V1V2-scaffold immunogens with advanced formulations for improved HIV vaccine efficacy.