Antibodies from Rabbits Immunized with HIV-1 Clade B SOSIP Trimers Can Neutralize Multiple Clade B Viruses by...

Area of Science:

• Immunology
• Virology
• Vaccine Development

Background:

• High human immunodeficiency virus type 1 (HIV-1) diversity hinders vaccine development.
• Current immunization strategies struggle to elicit broadly neutralizing antibodies (bNAbs).
• Understanding immune responses to HIV-1 envelope glycoprotein (Env) immunogens is crucial.

Purpose of the Study:

• To characterize monoclonal antibodies (MAbs) from rabbits immunized with HIV-1 Env SOSIP trimers.
• To investigate the neutralization mechanisms of elicited antibodies.
• To inform the design of next-generation HIV-1 vaccine candidates.

Main Methods:

• Immunization of rabbits with AMC008 Env SOSIP trimers.
• Isolation of antigen-specific MAbs using single B-cell sorting.
• Characterization of MAb binding and neutralization activity via electron microscopy and viral assays.

Main Results:

• Immunization elicited autologous and low-titer heterologous neutralizing responses.
• Seventeen trimer-reactive MAbs were isolated; four showed neutralization of autologous and other clade B viruses.
• Neutralizing MAbs bound to the gp41 subunit with unusual angles and induced Env trimer dissociation.

Conclusions:

• AMC008 SOSIP trimer immunization induced clade B-neutralizing MAbs targeting the gp41 subunit.
• Antibody-induced trimer destabilization is a key neutralization mechanism.
• Targeting trimer-dissociating epitopes may lead to improved HIV-1 vaccine immunogens.