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Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Shelly J Krebs | Young D Kwon | Chaim A Schramm | William H Law | Gina Donofrio | Kenneth H Zhou | Syna Gift | Vincent Dussupt | Ivelin S Georgiev | Sebastian Schätzle | Jonathan R McDaniel | Yen-Ting Lai | Mallika Sastry | Baoshan Zhang | Marissa C Jarosinski | Amy Ransier | Agnes L Chenine | 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 | Letzibeth Mendez | M Anthony Moody | Anne Marie O'Sullivan | Christopher 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
Immunity | 2019

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.

Pubmed ID: 30876875 RIS Download

Antibodies used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI131722
  • Agency: Intramural NIH HHS, United States
    Id: ZIA AI005024-17
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI131251
  • Agency: Intramural NIH HHS, United States
    Id: ZIA AI005022-17
  • Agency: NCI NIH HHS, United States
    Id: HHSN261200800001E
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008320

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