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

doi:10.1016/j.chom.2021.09.006

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

Cell Host Microbe. 2021 Nov 10;29(11):1634-1648.e5. doi: 10.1016/j.chom.2021.09.006. Epub 2021 Oct 4.

Authors

Rita E Chen¹, Brittany K Smith², John M Errico², David N Gordon³, Emma S Winkler¹, Laura A VanBlargan⁴, Chandni Desai², Scott A Handley², Kimberly A Dowd³, Emerito Amaro-Carambot³, M Jane Cardosa⁵, Carlos A Sariol⁶, Esper G Kallas⁷, Rafick-Pierre Sékaly⁸, Nikos Vasilakis⁹, Daved H Fremont¹⁰, Stephen S Whitehead³, Theodore C Pierson³, Michael S Diamond¹¹

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.

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.

Keywords: antibody; dengue; divergent; genotype; neutralization; pathogenesis; protection; serotype.

MeSH terms

Animals
Antibodies, Viral / blood
Antibodies, Viral / immunology
Antigens, Viral / immunology
Broadly Neutralizing Antibodies / blood
Broadly Neutralizing Antibodies / immunology*
Cross Protection*
Cross Reactions
Dengue / immunology*
Dengue / prevention & control
Dengue / virology
Dengue Vaccines / immunology*
Dengue Virus / genetics*
Dengue Virus / immunology*
Female
Genotype
Humans
Immunization, Passive
Immunogenicity, Vaccine
Macaca mulatta
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Serogroup
Viral Envelope Proteins / chemistry
Viral Envelope Proteins / immunology

Substances

Antibodies, Viral
Antigens, Viral
Broadly Neutralizing Antibodies
Dengue Vaccines
Viral Envelope Proteins

Abstract

MeSH terms

Substances

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