Dengue virus neutralization is modulated by IgG antibody subclass and Fcγ receptor subtype

W. W.Shanaka I. Rodrigo, Olivia K.T. Block, Christopher Lane, Soila Sukupolvi-Petty, Ana P. Goncalvez, Syd Johnson, Michael S. Diamond, Ching Juh Lai, Robert C. Rose, Xia Jin, Jacob J. Schlesinger

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Severe dengue virus (DENV) infection is epidemiologically linked to pre-existing anti-DENV antibodies acquired by maternal transfer or primary infection. A possible explanation is that DENV immune complexes evade neutralization by engaging Fcγ receptors (FcγR) on monocytes, natural targets for DENV in humans. Using epitope-matched humanized monoclonal antibodies (mAbs) and stable FcγR-transfected CV-1 cells, we found that DENV neutralization by IgG1, IgG3, and IgG4 mAbs was enhanced in high-affinity FcγRIA transfectants and diminished in low-affinity FcγRIIA transfectants, whereas neutralization by IgG2 mAbs (low-affinity ligands for both FcγRs) was diminished equally. In FcγR-negative Vero cells, IgG3 mAbs exhibited the strongest neutralizing activity and IgG2, the weakest. Our results demonstrate that DENV neutralization is modulated by the Fc region in an IgG subclass manner, likely through effects on virion and FcγR binding. Thus, the IgG antibody subclass profile generated by DENV infection or vaccination may independently influence the magnitude of the neutralizing response.

Original languageEnglish
Pages (from-to)175-182
Number of pages8
JournalVirology
Volume394
Issue number2
DOIs
StatePublished - Nov 25 2009

Keywords

  • Dengue virus
  • Fc receptor
  • Humanized monoclonal antibody
  • Virus neutralization

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    Rodrigo, W. W. S. I., Block, O. K. T., Lane, C., Sukupolvi-Petty, S., Goncalvez, A. P., Johnson, S., Diamond, M. S., Lai, C. J., Rose, R. C., Jin, X., & Schlesinger, J. J. (2009). Dengue virus neutralization is modulated by IgG antibody subclass and Fcγ receptor subtype. Virology, 394(2), 175-182. https://doi.org/10.1016/j.virol.2009.09.024