Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.
Krebs, Shelly J. 1,2,9; Kwon, Young D. 3,9; Schramm, Chaim A. 3,9; Law, William H. 3; Donofrio, Gina 1,2; Zhou, Kenneth H. 3; Gift, Syna 1,2; Dussupt, Vincent 1,2; Georgiev, Ivelin S. 4; Schatzle, Sebastian 5; McDaniel, Jonathan R. 5; Lai, Yen-Ting 3; Sastry, Mallika 3; Zhang, Baoshan 3; Jarosinski, Marissa C. 3; Ransier, Amy 3; Chenine, Agnes L. 1,2; Asokan, Mangaiarkarasi 3; Bailer, Robert T. 3; Bose, Meera 1,2; Cagigi, Alberto 3; Cale, Evan M. 3; Chuang, Gwo-Yu 3; Darko, Samuel 3; Driscoll, Jefferson I. 3; Druz, Aliaksandr 3; Gorman, Jason 3; Laboune, Farida 3; Louder, Mark K. 3; McKee, Krisha 3; Mendez, Letzibeth 1,2; Moody, Anthony M. 6; O'Sullivan, Anne Marie 1,2; Owen, Christopher 1,2; Peng, Dongjun 3; Rawi, Reda 3; Sanders-Buell, Eric 1,2; Shen, Chen-Hsiang 3; Shiakolas, Andrea R. 3; Stephens, Tyler 7; Tsybovsky, Yaroslav 7; Tucker, Courtney 1,2; Verardi, Raffaello 3; Wang, Keyun 3; Zhou, Jing 3; Zhou, Tongqing 3; Georgiou, George 5; Alam, Munir S. 6; Haynes, Barton F. 6; Rolland, Morgane 1,2; Matyas, Gary R. 1; Polonis, Victoria R. 1; McDermott, Adrian B. 3; Douek, Daniel C. 3; Shapiro, Lawrence 3,8; Tovanabutra, Sodsai 1,2; Michael, Nelson L. 1; Mascola, John R. 3; Robb, Merlin L. 1,2; Kwong, Peter D. 3,8,*; Doria-Rose, Nicole A. 3,10,*
[Article]
Immunity.
50(3):677-691,691e1-691e13, March 19, 2019.
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: 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.
* Multiple MPER-directed bNAb lineages developed in a single individual
* The broadest lineage belongs to the same antibody class as the 4E10 antibody
* Low levels of somatic hypermutation of the RV217-VRC42 lineage can impart breadth
* A multimeric immunogen activates VRC42 precursor B cells
(C) 2019Elsevier, Inc.
