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Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.

Chen-Hao Yeh, Stephen R Walsh, Ruth Parsons

Medrxiv : the Preprint Server for Health Sciences

|May 18, 2026

Summary

The CH505 trimer vaccine successfully induced broadly neutralizing antibodies (bnAbs) in humans, a key goal for HIV vaccine development. This immunogen primed diverse B cell responses, offering pathways for future HIV vaccine strategies.

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Area of Science:

Immunology
Vaccinology
Structural Biology

Background:

Inducing broadly neutralizing antibodies (bnAbs) is crucial for effective HIV vaccine development.
The CH505 transmitted/founder (TF) envelope trimer was designed to target specific B cell precursors.

Purpose of the Study:

To evaluate the immunogenicity and B cell responses elicited by the CH505 TF trimer in the HVTN300 clinical trial.
To assess the potential of the CH505 TF trimer to prime naïve B cell precursors for broadly neutralizing antibody development.

Main Methods:

Clinical trial (HVTN300) involving the administration of the CH505 TF trimer.
Analysis of autologous serum neutralizing activity and isolation of neutralizing B cells.
Cryo-electron microscopy (Cryo-EM) to determine antibody binding modes.

Main Results:

Autologous tier 2 serum neutralizing activity was observed in 9 of 11 vaccinees.
Neutralizing B cells were isolated from all participants.
CD4 binding site (CD4bs)-directed, CDRH3-binder bnAb precursors were identified in 73% of vaccinees, with one lineage showing nascent heterologous breadth.
Cryo-EM structures confirmed CD4bs CDRH3-binder engagement and revealed other vaccine-induced antibody specificities.

Conclusions:

The CH505 TF trimer successfully primed a diverse, polyclonal neutralizing B cell repertoire in humans.
The immunogen induced autologous tier 2 neutralizing B cell lineages in 100% of participants.
The study demonstrated the potential for sequential boosting strategies to achieve HIV bnAb breadth.