| Literature DB >> 30876875 |
Shelly J Krebs1, Young D Kwon2, Chaim A Schramm2, William H Law2, Gina Donofrio1, Kenneth H Zhou2, Syna Gift1, Vincent Dussupt1, Ivelin S Georgiev3, Sebastian Schätzle4, Jonathan R McDaniel4, Yen-Ting Lai2, Mallika Sastry2, Baoshan Zhang2, Marissa C Jarosinski2, Amy Ransier2, Agnes L Chenine1, Mangaiarkarasi Asokan2, Robert T Bailer2, Meera Bose1, Alberto Cagigi2, Evan M Cale2, Gwo-Yu Chuang2, Samuel Darko2, Jefferson I Driscoll2, Aliaksandr Druz2, Jason Gorman2, Farida Laboune2, Mark K Louder2, Krisha McKee2, Letzibeth Mendez1, M Anthony Moody5, Anne Marie O'Sullivan1, Christopher Owen1, Dongjun Peng2, Reda Rawi2, Eric Sanders-Buell1, Chen-Hsiang Shen2, Andrea R Shiakolas2, Tyler Stephens6, Yaroslav Tsybovsky6, Courtney Tucker1, Raffaello Verardi2, Keyun Wang2, Jing Zhou2, Tongqing Zhou2, George Georgiou4, S Munir Alam5, Barton F Haynes5, Morgane Rolland1, Gary R Matyas7, Victoria R Polonis7, Adrian B McDermott2, Daniel C Douek2, Lawrence Shapiro8, Sodsai Tovanabutra1, Nelson L Michael7, John R Mascola2, Merlin L Robb1, Peter D Kwong9, Nicole A Doria-Rose10.
Abstract
Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design. Published by Elsevier Inc.Entities:
Keywords: HIV envelope; neutralizing antibody; next-generation sequencing
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Year: 2019 PMID： 30876875 PMCID： PMC6555550 DOI： 10.1016/j.immuni.2019.02.008
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474