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

Chen RE 1 , Smith BK 2 , Errico JM 2 , Gordon DN 3 , Winkler ES 1 , VanBlargan LA 4 Show all authors , Desai C 2 , Handley SA 2 , Dowd KA 3 , Amaro-Carambot E 3 , Cardosa MJ 5 , Sariol CA 6 , Kallas EG 7 , Sékaly RP 8 , Vasilakis N 9 , Fremont DH 10 , Whitehead SS 3 , Pierson TC 3 , Diamond MS 11

Affiliations 

  • 1 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
  • 2 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
  • 3 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-9806, USA
  • 4 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
  • 5 Institute of Health and Community Medicine, Universiti Sarawak Malaysia (UNIMAS), Kota Samarahan, Sarawak 94300, Malaysia; Integrated Research Associates, San Rafael, CA 94903, USA
  • 6 Unit of Comparative Medicine, Caribbean Primate Research Center, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936-5067, USA
  • 7 Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil
  • 8 Department of Microbiology and Immunology, Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA
  • 9 Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vector-Borne and Zoonotic Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA
  • 10 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; The Andrew M. Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110-1010, USA
  • 11 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; The Andrew M. Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110-1010, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, Saint Louis, MO 63110-1010, USA. Electronic address: diamond@wusm.wustl.edu
Cell Host Microbe, 2021 Nov 10;29(11):1634-1648.e5.
PMID: 34610295 DOI: 10.1016/j.chom.2021.09.006

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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