Медицинская библиотека · medRxiv : the preprint server for health sciences · 2026

Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.

Yeh Chen-Hao, Walsh Stephen R, Parsons Ruth J, Zhang Qianyi E, Thakur Bhishem, Song Kijun, Liu Kejun, Kirshner Hélène Fradin, Van Ltallie Elizabeth, Clark Matthew, Hahn William O, Song Shengli, Lin Liwen, Huang Hsin-I, Lugo Jade, Quan Alex, Xue Yue, Chen Yue, Tuck Ryan, Mansouri Katayoun, Spence Taylor N, Laukaitis Helena A, Parks Rob, Barr Margaret, Schweer Elise, Levering Nicholas, Eaton Amanda, Shen Shaunna, Janowska Katarzyna, Ilevbare Victor, Johnson Graham, Wang Peng, Cain Derek, Arus-Altuz Aria, Donahue Elizabeth, Zhbannikov Ilya, Berry Madison, Venkatayogi Sravani, Martin Beem Joshua S, Hyrien Ollivier, Yu Pei-Chun, Polakowski Laura L, Tindale India, Yurdadon Claudio, Burnham Randy, Andriesen Jessica, Wagh Kshitij, Seaman Michael S, Walter Emmanuel B, Kelsoe Garnett, McElrath M Juliana, Corey Lawrence, Mayer Kenneth, Borrow Persephone, Williams Wilton, Saunders Kevin O, Wiehe Kevin, Montefiori David, Edwards Robert J, Acharya Priyamvada, Baden Lindsey, Haynes Barton F

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Induction of broadly neutralizing antibodies (bnAbs) remains a major goal of HIV vaccine development. In a Phase I clinical trial, we evaluated the immunogenicity of CH505 transmitted/founder (TF) envelope trimer designed to prime precursors of the heavy chain third complementarity determining region (CDRH3)-dominant class of CD4-binding site (CD4bs) HIV bnAbs. Neutralizing memory B-cell lineages were isolated from all vaccine recipients, including lineages targeting the CD4bs, V1/V3, and gp120/gp41 interface. Candidate CDRH3-dominant, CD4bs bnAb precursor lineages were identified in 73% of vaccinees, including one lineage that exhibited limited heterologous neutralization of global HIV-1 isolates. Structural analyses defined the modes of Env recognition by these three antibody classes. Together, these findings demonstrate that immunization with the CH505 TF trimer can prime a diverse, polyclonal repertoire of bnAb precursor lineages in humans, providing multiple starting points for sequential immunization strategies aimed at eliciting broadly neutralizing HIV-1 antibodies.

Для цитирования: Yeh Chen-Hao, Walsh Stephen R, Parsons Ruth J, Zhang Qianyi E, Thakur Bhishem, Song Kijun, Liu Kejun, Kirshner Hélène Fradin, Van Ltallie Elizabeth, Clark Matthew, Hahn William O, Song Shengli, Lin Liwen, Huang Hsin-I, Lugo Jade, Quan Alex, Xue Yue, Chen Yue, Tuck Ryan, Mansouri Katayoun, Spence Taylor N, Laukaitis Helena A, Parks Rob, Barr Margaret, Schweer Elise, Levering Nicholas, Eaton Amanda, Shen Shaunna, Janowska Katarzyna, Ilevbare Victor, Johnson Graham, Wang Peng, Cain Derek, Arus-Altuz Aria, Donahue Elizabeth, Zhbannikov Ilya, Berry Madison, Venkatayogi Sravani, Martin Beem Joshua S, Hyrien Ollivier, Yu Pei-Chun, Polakowski Laura L, Tindale India, Yurdadon Claudio, Burnham Randy, Andriesen Jessica, Wagh Kshitij, Seaman Michael S, Walter Emmanuel B, Kelsoe Garnett, McElrath M Juliana, Corey Lawrence, Mayer Kenneth, Borrow Persephone, Williams Wilton, Saunders Kevin O, Wiehe Kevin, Montefiori David, Edwards Robert J, Acharya Priyamvada, Baden Lindsey, Haynes Barton F. Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.. medRxiv : the preprint server for health sciences. 2026. DOI: 10.64898/2026.05.02.26352058.

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