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Targeted isolation of antibodies directed against major sites of SIV Env vulnerability

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Overview

authors

  • Mason, R. D.
  • Welles, H. C.
  • Adams, C.
  • Chakrabarti, B. K.
  • Gorman, J.
  • Zhou, T.
  • Nguyen, R.
  • O'Dell, S.
  • Lusvarghi, S.
  • Bewley, C. A.
  • Li, H.
  • Shaw, G. M.
  • Sheng, Z.
  • Shapiro, L.
  • Wyatt, Richard
  • Kwong, P. D.
  • Mascola, J. R.
  • Roederer, M.

publication date

  • April 2016

journal

  • PLoS Pathogens  Journal

abstract

  • The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-2(7312A). This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy.

subject areas

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Binding Sites
  • Epitopes
  • Gene Products, env
  • HIV Antibodies
  • Humans
  • Neutralization Tests
  • Simian Immunodeficiency Virus
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Identity

PubMed Central ID

  • PMC4827850

International Standard Serial Number (ISSN)

  • 1553-7366

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1005537

PubMed ID

  • 27064278
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Additional Document Info

volume

  • 12

issue

  • 4

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