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

• Type of Material: Article
• Authors: Rita E Chen, Washington University; Brittany K Smith, Washington University; John M Errico, Washington University; David N Gordon, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Emma S Winkler, Washington University; Laura A VanBlargan, Washington University; Chandni Desai, Washington University; Scott A Handley, Washington University; Kimberly A Dowd, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Emerito Amaro-Carambot, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Jane M Cardosa, Universiti Sarawak Malaysia (UNIMAS); Carlos A Sariol, University of Puerto Rico; Esper G Kallas, Universidade de São Paulo; Rafick-Pierre Sekaly, Emory University; Nikos Vasilakis, University of Texas Medical Branch; Daved H Fremont, Washington University; Stephen S Whitehead, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Theodore C Pierson, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Michael S Diamond, Washington University
• Language: English
• Date: 2021-11-10
• Publisher: CELL PRESS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2021.09.006
• Title of Journal or Parent Work: CELL HOST & MICROBE
• Volume: 29
• Issue: 11
• Start Page: 1634
• End Page: +
• Grant/Funding Information: This work was also supported by the Caribbean Primate Research Center (Grants P40 OD012217 and 2U42OD021458 from ORIP/OD/NIH). E.S.W. is supported by T32 AI007163.; This work was supported by NIAID contract 75N93019C00062 and NIH grants R01 AI073755, R01 AI125202, R21 AI145012, and U01 AI115577, a pilot grant by the Institute for Human Infection and Immunity (to N.V.), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (T.C.P. and S.S.W.)
• Keywords: HEMORRHAGIC-FEVER; ANTIBODY-DEPENDENT ENHANCEMENT; DISEASE SEVERITY; Parasitology; TYPE-2; PATHOGENESIS; MOUSE MODELS; Virology; IMPACTS; Microbiology; MEDIATED NEUTRALIZATION; IMMUNOGENICITY; INFECTION; Life Sciences & Biomedicine; Science & Technology

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.