The mechanism of differential neutralization of dengue serotype 3 strains by monoclonal antibody 8A1

Yang Zhou, S. Kyle Austin, Daved H. Fremont, Boyd L. Yount, Jeremy P. Huynh, Aravinda M. de Silva, Ralph S. Baric, William B. Messer

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

While previous studies have demonstrated that envelope (E) glycoprotein variation between dengue viruses (DENV) genotypes can influence antibody neutralization potency, the mechanisms of variable neutralization remain incompletely understood. Here we characterize epitope antibody interactions of a DENV-3 EDIII binding mouse mAb 8A1 which displays highly variable neutralizing activity against DENV-3 genotypes. Using a DENV-3 reverse genetics platform, we characterize ability of 8A1 to bind and neutralize naturally occurring DENV-3 E genotypic variant viruses. Introduction of single and multiple amino acid mutations into the parental clone background demonstrates that mutations at positions 301 and 383 on EDIII are responsible for 8A1 differential neutralization phenotypes. ELISA and surface plasmon resonance (SPR) studies indicate differences in binding are responsible for the variable neutralization. Variability at position 301 primarily determined binding difference through influencing antibody-EDIII dissociation rate. Our findings are relevant to many groups focusing on DENV EDIII as a vaccine target.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalVirology
Volume439
Issue number1
DOIs
StatePublished - Apr 25 2013

Keywords

  • Affinity
  • Antibody
  • Binding kinetic
  • Dengue
  • E domain III
  • Genotype
  • Neutralization

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    Zhou, Y., Austin, S. K., Fremont, D. H., Yount, B. L., Huynh, J. P., de Silva, A. M., Baric, R. S., & Messer, W. B. (2013). The mechanism of differential neutralization of dengue serotype 3 strains by monoclonal antibody 8A1. Virology, 439(1), 57-64. https://doi.org/10.1016/j.virol.2013.01.022