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Science. 2016 Sep 30;353(6307):1557-1560. Epub 2016 Sep 8.

Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Kymab Ltd, The Bennet Building (B930), Babraham Research Campus, Cambridge CB22 3AT, UK.
3
Kymab Ltd, The Bennet Building (B930), Babraham Research Campus, Cambridge CB22 3AT, UK. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
4
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA 02129, USA. burton@scripps.edu schief@scripps.edu.

Abstract

A major obstacle to a broadly neutralizing antibody (bnAb)-based HIV vaccine is the activation of appropriate B cell precursors. Germline-targeting immunogens must be capable of priming rare bnAb precursors in the physiological setting. We tested the ability of the VRC01-class bnAb germline-targeting immunogen eOD-GT8 60mer (60-subunit self-assembling nanoparticle) to activate appropriate precursors in mice transgenic for human immunoglobulin (Ig) loci. Despite an average frequency of, at most, about one VRC01-class precursor per mouse, we found that at least 29% of singly immunized mice produced a VRC01-class memory response, suggesting that priming generally succeeded when at least one precursor was present. The results demonstrate the feasibility of using germline targeting to prime specific and exceedingly rare bnAb-precursor B cells within a humanlike repertoire.

PMID:
27608668
PMCID:
PMC5404394
DOI:
10.1126/science.aah3945
[Indexed for MEDLINE]
Free PMC Article

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