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DOI 10.1126/science.add6502

Медицинская библиотека · Science (New York, N.Y.) · 2022

Vaccination induces HIV broadly neutralizing antibody precursors in humans.

Leggat David J, Cohen Kristen W, Willis Jordan R, Fulp William J, deCamp Allan C, Kalyuzhniy Oleksandr, Cottrell Christopher A, Menis Sergey, Finak Greg, Ballweber-Fleming Lamar, Srikanth Abhinaya, Plyler Jason R, Schiffner Torben, Liguori Alessia, Rahaman Farhad, Lombardo Angela, Philiponis Vincent, Whaley Rachael E, Seese Aaron, Brand Joshua, Ruppel Alexis M, Hoyland Wesley, Yates Nicole L, Williams LaTonya D, Greene Kelli, Gao Hongmei, Mahoney Celia R, Corcoran Martin M, Cagigi Alberto, Taylor Alison, Brown David M, Ambrozak David R, Sincomb Troy, Hu Xiaozhen, Tingle Ryan, Georgeson Erik, Eskandarzadeh Saman, Alavi Nushin, Lu Danny, Mullen Tina-Marie, Kubitz Michael, Groschel Bettina, Maenza Janine, Kolokythas Orpheus, Khati Nadia, Bethony Jeffrey, Crotty Shane, Roederer Mario, Karlsson Hedestam Gunilla B, Tomaras Georgia D, Montefiori David, Diemert David, Koup Richard A, Laufer Dagna S, McElrath M Juliana, McDermott Adrian B, Schief William R

Клиническое исследование I фазыСтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.

Для цитирования: Leggat David J, Cohen Kristen W, Willis Jordan R, Fulp William J, deCamp Allan C, Kalyuzhniy Oleksandr, Cottrell Christopher A, Menis Sergey, Finak Greg, Ballweber-Fleming Lamar, Srikanth Abhinaya, Plyler Jason R, Schiffner Torben, Liguori Alessia, Rahaman Farhad, Lombardo Angela, Philiponis Vincent, Whaley Rachael E, Seese Aaron, Brand Joshua, Ruppel Alexis M, Hoyland Wesley, Yates Nicole L, Williams LaTonya D, Greene Kelli, Gao Hongmei, Mahoney Celia R, Corcoran Martin M, Cagigi Alberto, Taylor Alison, Brown David M, Ambrozak David R, Sincomb Troy, Hu Xiaozhen, Tingle Ryan, Georgeson Erik, Eskandarzadeh Saman, Alavi Nushin, Lu Danny, Mullen Tina-Marie, Kubitz Michael, Groschel Bettina, Maenza Janine, Kolokythas Orpheus, Khati Nadia, Bethony Jeffrey, Crotty Shane, Roederer Mario, Karlsson Hedestam Gunilla B, Tomaras Georgia D, Montefiori David, Diemert David, Koup Richard A, Laufer Dagna S, McElrath M Juliana, McDermott Adrian B, Schief William R. Vaccination induces HIV broadly neutralizing antibody precursors in humans.. Science (New York, N.Y.). 2022. DOI: 10.1126/science.add6502.

Предметные рубрики MeSH

HumansAdjuvants, ImmunologicAIDS VaccinesBroadly Neutralizing AntibodiesHIV InfectionsVaccinationHIV AntibodiesGerm CellsB-LymphocytesMutationImmunoglobulin Light ChainsImmunoglobulin Heavy ChainsMaleFemaleAdult
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