A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits...

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Trimeric HIV-1 envelope (Env) immunogens are crucial for eliciting broadly neutralizing antibodies (bNAbs) and obscuring unfavorable epitopes.
• The RV144 trial underscored the significance of vaccine-induced antibodies targeting the HIV-1 Env V1V2 loop, particularly the V2 loop region, for protection.

Purpose of the Study:

• To evaluate the immunogenicity of a novel trimeric gp120 immunogen (cycP-gp120) in protein prime/boost and booster immunization strategies.
• To assess the capacity of cycP-gp120 to induce high-avidity, broadly cross-reactive anti-V1V2 antibodies and neutralization breadth against HIV-1.

Main Methods:

• Administered cycP-gp120 via protein prime/boost in rabbits and as a booster to DNA/modified vaccinia Ankara (MVA)-vaccinated rabbits and rhesus macaques.
• Assessed antibody titers, avidity, binding to V1V2 scaffolds, neutralization activity against tier-1A/1B HIV-1 isolates, and antibody-dependent cellular cytotoxicity (ADCC).

Main Results:

• Two cycP-gp120 protein immunizations in rabbits induced 100-fold higher IgG titers than monomeric gp120, requiring four immunizations for comparable titers.
• cycP-gp120 elicited enhanced neutralization against tier-1A/1B HIV-1 isolates and broader binding to V1V2 scaffolds from global isolates.
• Booster immunizations with cycP-gp120 in pre-vaccinated animals expanded gp70-V1V2-specific IgG, neutralization breadth, and ADCC activity.

Conclusions:

• cycP-gp120 is a potent HIV Env immunogen, inducing high-avidity anti-V1V2 antibodies and promoting neutralization breadth.
• The findings suggest cycP-gp120's potential as a vaccine candidate for inducing antibodies associated with reduced HIV-1 infection risk.