ArticleCommunications medicine2025
Convergence and divergence of B cell responses in two HIV-1 Env immunizations in Rhesus macaques.
Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSequential multivalent immunizations are used to counter diversity in rapidly mutating viruses. Here, we evaluated the effect of HIV-1 immunogen formats on the binding profile of memory B-cells elicited in two independent Rhesus macaque trials.
methodsIn one trial, female Rhesus macaques were immunized with a multiclade HIV-1 gp120 envelope glycoprotein (Env) cocktail and bled two weeks post final immunization. In another trial, male and female Rhesus macaques were sequentially immunized with clonally-related Env glycoproteins: Four immunogens were administered as non-stabilized gp140 Envs and the fifth as a specially stabilized gp140 Env trimer (SOSIP); animals were bled before and after SOSIP immunization. Immunogen-binding peripheral memory B-cells were sorted and cultured at limiting dilution. Culture supernatants were assessed by ELISA for binding to individual immunogens.
resultsIn the first trial, 81% (591/734) of B-cells cross-react with multiple Envs and most bind to all immunogens. In the second trial, 81% (331/410) of B-cells isolated before SOSIP administration react with all non-stabilized gp140 Env immunogens and 27% also cross-react with the yet-to-be-administered SOSIP-stabilized Env. However, after SOSIP administration, SOSIP-stabilized trimer-reactive B-cells increase to 86% (219/256) but most (82%) do not cross-react with the preceding immunogens.
conclusionsMulticlade and sequential regimens before SOSIP-stabilized Env immunization elicited B-cells that converge on shared epitopes. A change in immunogen format results in a divergent B-cell response that vastly fails to engage prior responses. Critically, B-cell priming with non-stabilized Env cannot modify the effect of the epitope immunodominance hierarchy in a SOSIP trimer. These results suggest that a change in immunogen format may cause off-target B-cell engagement, but also that B-cell repriming is possible despite pre-existing immunity.
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