5dt1
Crystal structure of human Fab CAP256-VRC26.25, a potent V1V2-directed HIV-1 broadly neutralizing antibody
Structural highlights
Publication Abstract from PubMedThe epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of twelve V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C infected donor at years 1, 2, and 4 of infection (N. A. Doria-Rose et al, Nature 50:55-62, 2014 doi:10.1038/nature13036). Here, we report the isolation and characterization of new members of the family, mostly from time points of peak serum breadth and potency. Thirteen antibodies were isolated from B cell culture, and eight using trimeric envelope probes for differential single B cell sorting. One of the new antibodies displayed 10-fold greater neutralization potency than previous published lineage members. This antibody, CAP256-VRC26.25, neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Among viruses neutralized, the median IC50 was 0.001 micrograms per ml. All 33 lineage members targeted a quaternary epitope focused on V2. While all known bNAbs targeting the V1V2 region interact with the N160 glycan, CAP256-VRC26 antibodies showed an inverse correlation of neutralization potency with dependence on this glycan. Overall, our results highlight the ongoing evolution within a single antibody lineage, and describe more potent and broadly neutralizing members with potential clinical utility, particularly in clade C-prevalent areas. IMPORTANCE: Studies of HIV-1 broadly neutralizing antibodies (bNAbs) provide valuable information for vaccine design, and the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of V1V2-directed neutralizing antibodies from an HIV-1 clade C infected donor. Here, we report the isolation and characterization of new members of the family, mostly from time points of peak serum breadth and potency. One of the new antibodies, CAP256-VRC26.25, displayed 10-fold greater neutralization potency than previous described lineage members. It neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency: a median IC50 of 0.001 micrograms per ml. Our results highlight the ongoing evolution within a single antibody lineage, and describe more potent and broadly neutralizing members with potential clinical utility, particularly in clade C-prevalent areas. A new member of the V1V2-directed CAP256-VRC26 lineage that shows increased breadth and exceptional potency.,Doria-Rose NA, Bhiman JN, Roark RS, Schramm CA, Gorman J, Chuang GY, Pancera M, Cale EM, Ernandes MJ, Louder MK, Asokan M, Bailer RT, Druz A, Fraschilla IR, Garrett NJ, Jarosinski M, Lynch RM, McKee K, O'Dell S, Pegu A, Schmidt SD, Staupe RP, Sutton MS, Wang K, Wibmer CK, Haynes BF, Abdool-Karim S, Shapiro L, Kwong PD, Moore PL, Morris L, Mascola JR J Virol. 2015 Oct 14. pii: JVI.01791-15. PMID:26468542[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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