Convergence and divergence of B cell responses in two HIV-1 Env immunizations in Rhesus macaques

Area of Science:

• Immunology
• Virology
• Vaccine Development

Background:

• Sequential multivalent immunizations are standard for combating rapidly mutating viruses like HIV-1.
• Understanding how different immunogen formats influence B-cell responses is crucial for effective vaccine design.

Purpose of the Study:

• To evaluate the impact of HIV-1 immunogen formats on the binding profiles of elicited memory B-cells.
• To compare B-cell responses generated by multiclade versus sequential Env glycoprotein immunizations in Rhesus macaques.

Main Methods:

• Two Rhesus macaque trials were conducted using different HIV-1 envelope glycoprotein (Env) immunization strategies.
• Peripheral memory B-cells were sorted, cultured, and supernatants were analyzed by ELISA for binding to various Env immunogens.

Main Results:

• In the first trial, a high percentage of B-cells cross-reacted with multiple Envs.
• In the second trial, sequential immunization with non-stabilized gp140 Envs elicited B-cells reactive to all prior immunogens, but the introduction of a stabilized SOSIP trimer led to a divergent B-cell response.
• Post-SOSIP immunization, a significant increase in SOSIP-reactive B-cells was observed, with limited cross-reactivity to preceding immunogens.

Conclusions:

• Sequential immunogen regimens can elicit B-cells that converge on shared epitopes.
• A change in immunogen format, particularly to a stabilized SOSIP trimer, can result in a divergent B-cell response that does not engage prior responses.
• B-cell priming with non-stabilized Env does not alter the epitope immunodominance hierarchy in a SOSIP trimer, but B-cell repriming is feasible despite existing immunity.