A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Nat Immunol. 2015 Feb;16(2):170-177. doi: 10.1038/ni.3058. Epub 2014 Dec 15.

Abstract

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / isolation & purification*
  • Biological Assay
  • Cell Line
  • Dengue / blood
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoblotting
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Viral Envelope Proteins
  • glycoprotein E, dengue virus type 4