Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.
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.
Krebs, SJ; Kwon, YD; Schramm, CA; Law, WH; Donofrio, G; Zhou, KH; Gift, S; Dussupt, V; Georgiev, IS; Schätzle, S; McDaniel, JR; Lai, Y-T; Sastry, M; Zhang, B; Jarosinski, MC; Ransier, A; Chenine, AL; Asokan, M; Bailer, RT; Bose, M; Cagigi, A; Cale, EM; Chuang, G-Y; Darko, S; Driscoll, JI; Druz, A; Gorman, J; Laboune, F; Louder, MK; McKee, K; Mendez, L; Moody, MA; O'Sullivan, AM; Owen, C; Peng, D; Rawi, R; Sanders-Buell, E; Shen, C-H; Shiakolas, AR; Stephens, T; Tsybovsky, Y; Tucker, C; Verardi, R; Wang, K; Zhou, J; Zhou, T; Georgiou, G; Alam, SM; Haynes, BF; Rolland, M; Matyas, GR; Polonis, VR; McDermott, AB; Douek, DC; Shapiro, L; Tovanabutra, S; Michael, NL; Mascola, JR; Robb, ML; Kwong, PD; Doria-Rose, NA
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