Jordan R Willis, Madhu Prabhakaran, Michelle Muthui, Ansuya Naidoo, Troy Sincomb, Weiwei Wu, Christopher A Cottrell, Elise Landais, Allan C deCamp, Nahid R Keshavarzi, Oleksandr Kalyuzhniy, Jeong Hyun Lee, Linda M Murungi, Wilfrida A Ogonda, Nicole L Yates, Martin M Corcoran, Swastik Phulera, Joel Musando, Amanda Tsai, Gabrielle Lemire, Yiakon Sein, Michael Muteti, Praveen Alamuri, Jennifer A Bohl, Drienna Holman, Sunny Himansu, Brett Leav, Caroline Reuter, Li-An Lin, Baoyu Ding, Chunla He, Walter L Straus, Kellie J MacPhee, Isabel Regadas, Diana V Nyabundi, Ruth Chirchir, Aggrey Anzala, John N Kimotho, Caleb Kibet, Kelli Greene, Hongmei Gao, Erica Beatman, Kiara Benson, Dominick Laddy, David M Brown, Rhianna Bronson, Jalen Baptiste, Suprabhath Gajjala, Zahra Rikhtegaran-Tehrani, Alison Benner, Mukundhan Ramaswami, Danny Lu, Nushin Alavi, Sonya Amirzehni, Michael Kubitz, Ryan Tingle, Erik Georgeson, Nicole Phelps, Yumiko Adachi, Alessia Liguori, Claudia Flynn, Katherine McKenney, Xiaoya Zhou, D Collins Owuor, Sharon Owuor, Soo-Young Kim, Michael Duff, Ju Yeong Kim, Grace Gibson, Sabyasachi Baboo, Jolene Diedrich, Torben Schiffner, Marisa Shields, Mabela Matsoso, Jennifer Santos, Kristen Syvertsen, Allison Kennedy, Melissa Schroeter, Johan Vekemans, John Yates, James C Paulson, Ollivier Hyrien, Adrian B McDermott, Pholo Maenetje, Julien Nyombayire, Etienne Karita, Rosine Ingabire, Vinodh Edward, Vincent Muturi-Kioi, Janine Maenza, Adrienne E Shapiro, M Juliana McElrath, Srilatha Edupuganti, Barbara S Taylor, David Diemert, Gabriel Ozorowski, Richard A Koup, David Montefiori, Andrew B Ward, Gunilla Karlsson Hedestam, Georgia Tomaras, Devin J Hunt, Daniel Muema, Devin Sok, Dagna S Laufer, Sarah F Andrews, Eunice W Nduati, William R Schief
{"title":"Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.","authors":"Jordan R Willis, Madhu Prabhakaran, Michelle Muthui, Ansuya Naidoo, Troy Sincomb, Weiwei Wu, Christopher A Cottrell, Elise Landais, Allan C deCamp, Nahid R Keshavarzi, Oleksandr Kalyuzhniy, Jeong Hyun Lee, Linda M Murungi, Wilfrida A Ogonda, Nicole L Yates, Martin M Corcoran, Swastik Phulera, Joel Musando, Amanda Tsai, Gabrielle Lemire, Yiakon Sein, Michael Muteti, Praveen Alamuri, Jennifer A Bohl, Drienna Holman, Sunny Himansu, Brett Leav, Caroline Reuter, Li-An Lin, Baoyu Ding, Chunla He, Walter L Straus, Kellie J MacPhee, Isabel Regadas, Diana V Nyabundi, Ruth Chirchir, Aggrey Anzala, John N Kimotho, Caleb Kibet, Kelli Greene, Hongmei Gao, Erica Beatman, Kiara Benson, Dominick Laddy, David M Brown, Rhianna Bronson, Jalen Baptiste, Suprabhath Gajjala, Zahra Rikhtegaran-Tehrani, Alison Benner, Mukundhan Ramaswami, Danny Lu, Nushin Alavi, Sonya Amirzehni, Michael Kubitz, Ryan Tingle, Erik Georgeson, Nicole Phelps, Yumiko Adachi, Alessia Liguori, Claudia Flynn, Katherine McKenney, Xiaoya Zhou, D Collins Owuor, Sharon Owuor, Soo-Young Kim, Michael Duff, Ju Yeong Kim, Grace Gibson, Sabyasachi Baboo, Jolene Diedrich, Torben Schiffner, Marisa Shields, Mabela Matsoso, Jennifer Santos, Kristen Syvertsen, Allison Kennedy, Melissa Schroeter, Johan Vekemans, John Yates, James C Paulson, Ollivier Hyrien, Adrian B McDermott, Pholo Maenetje, Julien Nyombayire, Etienne Karita, Rosine Ingabire, Vinodh Edward, Vincent Muturi-Kioi, Janine Maenza, Adrienne E Shapiro, M Juliana McElrath, Srilatha Edupuganti, Barbara S Taylor, David Diemert, Gabriel Ozorowski, Richard A Koup, David Montefiori, Andrew B Ward, Gunilla Karlsson Hedestam, Georgia Tomaras, Devin J Hunt, Daniel Muema, Devin Sok, Dagna S Laufer, Sarah F Andrews, Eunice W Nduati, William R Schief","doi":"10.1126/science.adr8382","DOIUrl":null,"url":null,"abstract":"<p><p>A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States and IAVI-G003 in Rwanda and South Africa, we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI-G002). The vaccines were generally safe and well tolerated, except 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. The results establish clinical proof of concept that heterologous boosting can advance bnAb-precursor maturation and demonstrate bnAb priming in Africa where the HIV burden is highest.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":" ","pages":"eadr8382"},"PeriodicalIF":44.7000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1126/science.adr8382","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States and IAVI-G003 in Rwanda and South Africa, we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI-G002). The vaccines were generally safe and well tolerated, except 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. The results establish clinical proof of concept that heterologous boosting can advance bnAb-precursor maturation and demonstrate bnAb priming in Africa where the HIV burden is highest.
期刊介绍：
Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research.
Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated.
Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
