Медицинская библиотека · Science (New York, N.Y.) · 2025

Precise targeting of HIV broadly neutralizing antibody precursors in humans.

Caniels Tom G, Prabhakaran Madhu, Ozorowski Gabriel, MacPhee Kellie J, Wu Weiwei, van der Straten Karlijn, Agrawal Sashank, Derking Ronald, Reiss Emma I M M, Millard Katrina, Turroja Martina, Desrosiers Aimee, Bethony Jeffrey, Malkin Elissa, Liesdek Marinus H, van der Veen Annelou, Klouwens Michelle, Snitselaar Jonne L, Bouhuijs Joey H, Bronson Rhianna, Jean-Baptiste Jalen, Gajjala Suprabhath, Rikhtegaran Tehrani Zahra, Benner Alison, Ramaswami Mukundhan, Duff Michael O, Liu Yung-Wen, Sato Alicia H, Kim Ju Yeong, Baken Isabel J L, Mendes Silva Catarina, Bijl Tom P L, van Rijswijk Jacqueline, Burger Judith A, Cupo Albert, Yasmeen Anila, Phulera Swastik, Lee Wen-Hsin, Randall Kipchoge N, Zhang Shiyu, Corcoran Martin M, Regadas Isabel, Sullivan Alex C, Brown David M, Bohl Jennifer A, Greene Kelli M, Gao Hongmei, Yates Nicole L, Sawant Sheetal, Prins Jan M, Kootstra Neeltje A, Kaminsky Stephen M, Barin Burc, Rahaman Farhad, Meller Margaret, Philiponis Vince, Laufer Dagna S, Lombardo Angela, Mwoga Lindsey, Shotorbani Solmaz, Holman Drienna, Koup Richard A, Klasse Per Johan, Karlsson Hedestam Gunilla B, Tomaras Georgia D, van Gils Marit J, Montefiori David C, McDermott Adrian B, Hyrien Ollivier, Moore John P, Wilson Ian A, Ward Andrew B, Diemert David J, de Bree Godelieve J, Andrews Sarah F, Caskey Marina, Sanders Rogier W

СтатьяКлиническое исследование I фазыРандомизированное исследованиеПеревод пока не подготовлен

Аннотация

A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01B, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, which target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.

Для цитирования: Caniels Tom G, Prabhakaran Madhu, Ozorowski Gabriel, MacPhee Kellie J, Wu Weiwei, van der Straten Karlijn, Agrawal Sashank, Derking Ronald, Reiss Emma I M M, Millard Katrina, Turroja Martina, Desrosiers Aimee, Bethony Jeffrey, Malkin Elissa, Liesdek Marinus H, van der Veen Annelou, Klouwens Michelle, Snitselaar Jonne L, Bouhuijs Joey H, Bronson Rhianna, Jean-Baptiste Jalen, Gajjala Suprabhath, Rikhtegaran Tehrani Zahra, Benner Alison, Ramaswami Mukundhan, Duff Michael O, Liu Yung-Wen, Sato Alicia H, Kim Ju Yeong, Baken Isabel J L, Mendes Silva Catarina, Bijl Tom P L, van Rijswijk Jacqueline, Burger Judith A, Cupo Albert, Yasmeen Anila, Phulera Swastik, Lee Wen-Hsin, Randall Kipchoge N, Zhang Shiyu, Corcoran Martin M, Regadas Isabel, Sullivan Alex C, Brown David M, Bohl Jennifer A, Greene Kelli M, Gao Hongmei, Yates Nicole L, Sawant Sheetal, Prins Jan M, Kootstra Neeltje A, Kaminsky Stephen M, Barin Burc, Rahaman Farhad, Meller Margaret, Philiponis Vince, Laufer Dagna S, Lombardo Angela, Mwoga Lindsey, Shotorbani Solmaz, Holman Drienna, Koup Richard A, Klasse Per Johan, Karlsson Hedestam Gunilla B, Tomaras Georgia D, van Gils Marit J, Montefiori David C, McDermott Adrian B, Hyrien Ollivier, Moore John P, Wilson Ian A, Ward Andrew B, Diemert David J, de Bree Godelieve J, Andrews Sarah F, Caskey Marina, Sanders Rogier W. Precise targeting of HIV broadly neutralizing antibody precursors in humans.. Science (New York, N.Y.). 2025. DOI: 10.1126/science.adv5572.

Предметные рубрики MeSH

Humans Adjuvants, Immunologic AIDS Vaccines Antibodies, Monoclonal B-Lymphocytes Broadly Neutralizing Antibodies CD4 Antigens Double-Blind Method env Gene Products, Human Immunodeficiency Virus HIV Antibodies HIV Infections HIV-1 Somatic Hypermutation, Immunoglobulin

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