Implications of a highly divergent dengue virus strain for cross-neutralization, protection, and vaccine immunity

Rita E. Chen, Brittany K. Smith, John M. Errico, David N. Gordon, Emma S. Winkler, Laura A. VanBlargan, Chandni Desai, Scott A. Handley, Kimberly A. Dowd, Emerito Amaro-Carambot, M. Jane Cardosa, Carlos A. Sariol, Esper G. Kallas, Rafick Pierre Sékaly, Nikos Vasilakis, Daved H. Fremont, Stephen S. Whitehead, Theodore C. Pierson, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1–4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.

Original languageEnglish
Pages (from-to)1634-1648.e5
JournalCell Host and Microbe
Issue number11
StatePublished - Nov 10 2021


  • antibody
  • dengue
  • divergent
  • genotype
  • neutralization
  • pathogenesis
  • protection
  • serotype


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