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Science (New York, N.Y.) · 2025

Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.

СтатьяКлиническое исследование I фазыРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Willis Jordan R, Prabhakaran Madhu, Muthui Michelle, Naidoo Ansuya, Sincomb Troy, Wu Weiwei, Cottrell Christopher A, Landais Elise, deCamp Allan C, Keshavarzi Nahid R, Kalyuzhniy Oleksandr, Lee Jeong Hyun, Murungi Linda M, Ogonda Wilfrida A, Yates Nicole L, Corcoran Martin M, Phulera Swastik, Musando Joel, Tsai Amanda, Lemire Gabrielle, Sein Yiakon, Muteti Michael, Alamuri Praveen, Bohl Jennifer A, Holman Drienna, Himansu Sunny, Leav Brett, Reuter Caroline, Lin Li-An, Ding Baoyu, He Chunla, Straus Walter L, MacPhee Kellie J, Regadas Isabel, Nyabundi Diana V, Chirchir Ruth, Anzala Omu, Kimotho John N, Kibet Caleb, Greene Kelli, Gao Hongmei, Beatman Erica, Benson Kiara, Laddy Dominick, Brown David M, Bronson Rhianna, Jean-Baptiste Jalen, Gajjala Suprabhath, Rikhtegaran-Tehrani Zahra, Benner Alison, Ramaswami Mukundhan, Lu Danny, Alavi Nushin, Amirzehni Sonya, Kubitz Michael, Tingle Ryan, Georgeson Erik, Phelps Nicole, Adachi Yumiko, Liguori Alessia, Flynn Claudia, McKenney Katherine, Zhou Xiaoya, Owuor D Collins, Owuor Sharon A, Kim Soo-Young, Duff Michael, Kim Ju Yeong, Gibson Grace, Baboo Sabyasachi, Diedrich Jolene, Schiffner Torben, Shields Marisa, Matsoso Mabela, Santos Jennifer, Syvertsen Kristen, Kennedy Allison, Schroeter Melissa, Vekemans Johan, Yates John R, Paulson James C, Hyrien Ollivier, McDermott Adrian B, Maenetje Pholo, Nyombayire Julien, Karita Etienne, Ingabire Rosine, Edward Vinodh, Muturi-Kioi Vincent, Maenza Janine, Shapiro Adrienne E, McElrath M Juliana, Edupuganti Srilatha, Taylor Barbara S, Diemert David, Ozorowski Gabriel, Koup Richard A, Montefiori David, Ward Andrew B, Karlsson Hedestam Gunilla B, Tomaras Georgia, Hunt Devin J, Muema Daniel, Sok Devin, Laufer Dagna S, Andrews Sarah F, Nduati Eunice W, Schief William R

Аннотация

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 (IAVI, International Aids Vaccine Initiative), 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 that 18% of IAVI G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM; heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development; and elicited antibodies exhibited precise bnAb structural mimicry. 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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты