A new quaternary structure epitope on dengue virus serotype 2 is the target of durable type-specific neutralizing antibodies

E. N. Gallichotte, D. G. Widman, B. L. Yount, W. M. Wahala, A. Durbin, S. Whitehead, C. A. Sariol, J. E. Crowe, A. M. De Silva, R. S. Barica

Research output: Contribution to journalArticle

Abstract

Dengue virus serotype 2 (DENV2) is widespread and responsible for severe epidemics. While primary DENV2 infections stimulate serotype-specific protective responses, a leading vaccine failed to induce a similar protective response. Using human monoclonal antibodies (hMAbs) isolated from dengue cases and structure-guided design of a chimeric DENV, here we describe the major site on the DENV2 envelope (E) protein targeted by neutralizing antibodies. DENV2-specific neutralizing hMAb 2D22 binds to a quaternary structure epitope. We engineered and recovered a recombinant DENV4 that displayed the 2D22 epitope. DENV2 neutralizing antibodies in people exposed to infection or a live vaccine tracked with the 2D22 epitope on the DENV4/2 chimera. The chimera remained sensitive to DENV4 antibodies, indicating that the major neutralizing epitopes on DENV2 and-4 are at different sites. The ability to transplant a complex epitope between DENV serotypes demonstrates a hitherto underappreciated structural flexibility in flaviviruses, which could be harnessed to develop new vaccines and diagnostics.

Original languageEnglish (US)
Article numbere01461-15
JournalmBio
Volume6
Issue number5
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Virology

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    Gallichotte, E. N., Widman, D. G., Yount, B. L., Wahala, W. M., Durbin, A., Whitehead, S., Sariol, C. A., Crowe, J. E., De Silva, A. M., & Barica, R. S. (2015). A new quaternary structure epitope on dengue virus serotype 2 is the target of durable type-specific neutralizing antibodies. mBio, 6(5), [e01461-15]. https://doi.org/10.1128/mBio.01461-15