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2G12-expressing B cell lines may aid in HIV carbohydrate vaccine design strategies

Academic Article
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Overview

authors

  • Doores, K. J.
  • Huber, M.
  • Le, K. M.
  • Wang, Sheng-Kai
  • Doyle-Cooper, C.
  • Cooper, A.
  • Pantophlet, R.
  • Wong, Chi-Huey
  • Nemazee, David
  • Burton, Dennis

publication date

  • February 2013

journal

  • Journal of Virology  Journal

abstract

  • The highly conserved cluster of high-mannose glycans on the HIV-1 envelope glycoprotein, gp120, has been highlighted as a target for neutralizing antibodies. 2G12, the first HIV-1 antiglycan neutralizing antibody described, binds with an unusual domain-exchanged structure that creates a high-affinity multivalent binding surface. It is an interesting challenge for rational vaccine design to generate immunogens capable of eliciting domain-exchanged 2G12-like responses. We recently showed that di-mannose recognition by the variable domains of 2G12 is independent of domain exchange but that exchange is critical for virus neutralization. Carbohydrate-based immunogens aimed at inducing 2G12-like antibodies may need to drive both di-mannose recognition and domain exchange through interactions with B cell receptors. Here we assessed the ability of such immunogens to activate mouse B cell lines displaying domain-exchanged wild-type 2G12 (2G12 WT), a non-domain-exchanged Y-shaped variant (2G12 I19R), and germ line 2G12 (2G12 gl). We show that several immunogens, including heat-killed yeast and bacteria, can activate both 2G12 WT and 2G12 I19R B cells. However, only discrete clusters of high-mannose glycans, as on recombinant forms of the HIV-1 envelope trimer and oligodendrons, activate 2G12 WT B cells. Furthermore, no immunogen tested activated 2G12 gl cells. Our results support the hypothesis that in order to drive domain exchange of an antimannose antibody response, a boost with an immunogen displaying discrete clusters of high-mannose glycans not recognized by conventional Y-shaped antibodies will be required. Additionally, a molecule capable of activating 2G12 gl cells might also be required. The results highlight broadly neutralizing antibody-expressing mouse B cells as potentially useful tools for carbohydrate immunogen screening.

subject areas

  • AIDS Vaccines
  • Animals
  • Antibodies, Monoclonal
  • B-Lymphocytes
  • Carbohydrates
  • Cell Line
  • Drug Discovery
  • Gene Expression
  • HIV Envelope Protein gp120
  • HIV-1
  • Lymphocyte Activation
  • Mice
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Identity

PubMed Central ID

  • PMC3571453

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.02820-12

PubMed ID

  • 23221565
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Additional Document Info

start page

  • 2234

end page

  • 2241

volume

  • 87

issue

  • 4

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