Dengue and Zika Virus Cross-Reactive Human Monoclonal Antibodies Protect against Spondweni Virus Infection and Pathogenesis in Mice
Vanessa Salazar,
Brett W. Jagger,
Juthathip Mongkolsapaya,
Katherine E. Burgomaster,
Wanwisa Dejnirattisai,
Emma S. Winkler,
Estefania Fernandez,
Christopher A. Nelson,
Daved H. Fremont,
Theodore C. Pierson,
James E. Crowe, Jr.,
Gavin R. Screaton,
Michael S. Diamond
Affiliations
Vanessa Salazar
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
Brett W. Jagger
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
Juthathip Mongkolsapaya
Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok 10700, Thailand
Katherine E. Burgomaster
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
Wanwisa Dejnirattisai
Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
Emma S. Winkler
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Estefania Fernandez
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Christopher A. Nelson
Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Daved H. Fremont
Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Theodore C. Pierson
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
James E. Crowe, Jr.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Gavin R. Screaton
Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
Michael S. Diamond
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA; Corresponding author
Summary: Spondweni virus (SPOV) is the flavivirus that is most closely related to Zika virus (ZIKV). Although SPOV causes sporadic human infections in Africa, recently it was found in Culex mosquitoes in Haiti. To investigate the pathogenic spectrum of SPOV, we developed infection models in mice. Although two SPOV strains failed to cause disease in immunocompetent mice, each accumulated in the brain, spleen, eye, testis, and kidney when type I interferon signaling was blocked and unexpectedly caused infection, immune cell infiltration, and swelling in the ankle. In pregnant mice, SPOV replicated in the placenta and fetus but did not cause placental insufficiency or microcephaly. We identified human antibodies from ZIKV or DENV immune subjects that neutralized SPOV infection and protected against lethal challenge. Our experiments describe similarities and differences in clinical syndromes between SPOV and ZIKV and suggest that their serological relatedness has implications for antibody therapeutics and flavivirus vaccine development. : Salazar et al. show that SPOV, the flavivirus most closely related to ZIKV, infects mice when type I interferon signaling is blocked. SPOV causes ankle swelling and infection in the foot, which is more typical of alphaviruses. Human antibodies from ZIKV or DENV subjects protect against lethal SPOV challenge. Keywords: flavivirus, pathogenesis, Spondweni virus, Zika virus, Dengue virus, arthritis, antibody therapy, immunity
