[PDF][PDF] Longitudinal analysis reveals early development of three MPER-directed neutralizing antibody lineages from an HIV-1-infected individual

SJ Krebs, YD Kwon, CA Schramm, WH Law… - Immunity, 2019 - cell.com
SJ Krebs, YD Kwon, CA Schramm, WH Law, G Donofrio, KH Zhou, S Gift, V Dussupt…
Immunity, 2019cell.com
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 …
Summary
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.
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