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 Messer

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

Dengue Virus
Dengue
Monoclonal Antibodies
Genotype
Immunologic Techniques
Reverse Genetics
Mutation
Surface Plasmon Resonance
Antibodies
Serogroup
Epitopes
Glycoproteins
Vaccines
Clone Cells
Enzyme-Linked Immunosorbent Assay
Viruses
Phenotype
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Virology

Cite this

Zhou, Y., Austin, S. K., Fremont, D. H., Yount, B. L., Huynh, J. P., de Silva, A. M., ... Messer, W. (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

The mechanism of differential neutralization of dengue serotype 3 strains by monoclonal antibody 8A1. / Zhou, Yang; Austin, S. Kyle; Fremont, Daved H.; Yount, Boyd L.; Huynh, Jeremy P.; de Silva, Aravinda M.; Baric, Ralph S.; Messer, William.

In: Virology, Vol. 439, No. 1, 25.04.2013, p. 57-64.

Research output: Contribution to journalArticle

Zhou, Y, Austin, SK, Fremont, DH, Yount, BL, Huynh, JP, de Silva, AM, Baric, RS & Messer, W 2013, 'The mechanism of differential neutralization of dengue serotype 3 strains by monoclonal antibody 8A1', Virology, vol. 439, no. 1, pp. 57-64. https://doi.org/10.1016/j.virol.2013.01.022
Zhou, Yang ; Austin, S. Kyle ; Fremont, Daved H. ; Yount, Boyd L. ; Huynh, Jeremy P. ; de Silva, Aravinda M. ; Baric, Ralph S. ; Messer, William. / The mechanism of differential neutralization of dengue serotype 3 strains by monoclonal antibody 8A1. In: Virology. 2013 ; Vol. 439, No. 1. pp. 57-64.
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