作者
Shelly J. Krebs,Young Do Kwon,Chaim A. Schramm,William H. Law,Gina Donofrio,Kenneth H. Zhou,Syna Kuriakose Gift,Vincent Dussupt,Ivelin S. Georgiev,Sebastian Schätzle,Jonathan R. McDaniel,Yen‐Ting Lai,Mallika Sastry,Baoshan Zhang,Marissa Jarosinski,Amy Ransier,Agnès L. Chénine,Mangaiarkarasi Asokan,Robert T. Bailer,Meera Bose,Alberto Cagigi,Evan M. Cale,Gwo‐Yu Chuang,Samuel Darko,Jefferson I. Driscoll,Aliaksandr Druz,Jason Gorman,Farida Laboune,Mark K. Louder,Krisha McKee,Lídice Méndez,M. Anthony Moody,Anne Marie O’Sullivan,Christopher L. Owen,Dongjun Peng,Reda Rawi,Eric Sanders‐Buell,Chen‐Hsiang Shen,Andrea R. Shiakolas,Tyler Stephens,Yaroslav Tsybovsky,Courtney Tucker,Raffaello Verardi,Keyun Wang,Jing Zhou,Tongqing Zhou,George Georgiou,S. Munir Alam,Barton F. Haynes,Morgane Rolland,Gary R. Matyas,Victoria R. Polonis,Adrian B. McDermott,Daniel C. Douek,Lawrence Shapiro,Sodsai Tovanabutra,Nelson L. Michael,John R. Mascola,Merlin L. Robb,Peter D. Kwong,Nicole A. Doria‐Rose
摘要
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.