Vaccine elicitation of high mannose-dependent neutralizing antibodies against the V3-glycan broadly neutralizing epitope in nonhuman primates Journal Article

   


Authors: Saunders, K. O.; Nicely, N. I.; Wiehe, K.; Bonsignori, M.; Meyerhoff, R. R.; Parks, R.; Walkowicz, W. E.; Aussedat, B.; Wu, N. R.; Cai, F.; Vohra, Y.; Park, P. K.; Eaton, A.; Go, E. P.; Sutherland, L. L.; Scearce, R. M.; Barouch, D. H.; Zhang, R.; Von Holle, T.; Overman, R. G.; Anasti, K.; Sanders, R. W.; Moody, M. A.; Kepler, T. B.; Korber, B.; Desaire, H.; Santra, S.; Letvin, N. L.; Nabel, G. J.; Montefiori, D. C.; Tomaras, G. D.; Liao, H. X.; Alam, S. M.; Danishefsky, S. J.; Haynes, B. F.
Article Title: Vaccine elicitation of high mannose-dependent neutralizing antibodies against the V3-glycan broadly neutralizing epitope in nonhuman primates
Abstract: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans—a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors. © 2017 The Author(s)
Keywords: vaccination; hiv; glycan; long-term immunization; v3 glycan
Journal Title: Cell Reports
Volume: 18
Issue: 9
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2017-02-28
Start Page: 2175
End Page: 2188
Language: English
DOI: 10.1016/j.celrep.2017.02.003
PROVIDER: scopus
PUBMED: 28249163
PMCID: PMC5408352
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014123206&doi=10.1016%2fj.celrep.2017.02.003&partnerID=40&md5=c16d83cdab52e4e2abdc991dc3dbff1b
Notes: Article -- Export Date: 3 April 2017 -- Source: Scopus
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MSK Authors
  1. Peter Kinam Park
    10 Park
  2. Baptiste Aussedat
    17 Aussedat
  3. Samuel J Danishefsky
    539 Danishefsky
  4. Yusufbhai Usmanbhai Vohra
    6 Vohra
  5. William Walkowicz
    9 Walkowicz
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