Early clonal dominance at priming sets the trajectory for broad HIV serum neutralization

Early clonal dominance after Q23-APEX-GT2 priming in outbred rhesus macaques is linked to broad HIV-1 serum neutralization, including one animal neutralizing ~70% of tested viruses.

• Why it matters: Determinants of how germline-targeting vaccines induce broadly neutralizing antibodies are unclear, limiting rational design of HIV vaccine regimens.
• What they did: Immunized rhesus macaques were infected with CAP256.SU SHIV, and breadth was related to early autologous neutralization and B-cell priming efficiency; lineage tracing and structural analyses assessed V2-apex B-cell recruitment and maturation.
• The result: Four of six macaques developed heterologous serum neutralization breadth, and early dominance of one or two long-CDRH3 V2-apex clones predicted breadth, while non-neutralizing lineages failed due to unfavorable V2-apex approach angles and limited glycan engagement.