Format

Send to

Choose Destination
See comment in PubMed Commons below
Immunity. 2016 May 17;44(5):1215-26. doi: 10.1016/j.immuni.2016.04.016.

Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.

Author information

1
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA.
2
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
5
Monogram Biosciences Inc., San Francisco, CA, 94080, USA.
6
Zambia-Emory HIV Research Project, Lusaka, Zambia.
7
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
8
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
9
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
10
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA; Institut de Biologie Structurale, Université Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France. Electronic address: poignard@scripps.edu.

Abstract

The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways.

Comment in

PMID:
27192579
PMCID:
PMC5003182
DOI:
10.1016/j.immuni.2016.04.016
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center