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Publication Abstract from PubMed

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.

Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.,Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schatzle S, McDaniel JR, Lai YT, Sastry M, Zhang B, Jarosinski MC, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang GY, 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 CH, 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 Immunity. 2019 Mar 19;50(3):677-691.e13. doi: 10.1016/j.immuni.2019.02.008. Epub , 2019 Mar 12. PMID:30876875^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.