Dengue and Zika Virus Cross-Reactive Human Monoclonal Antibodies Protect against Spondweni Virus Infection and Pathogenesis in Mice
Year: 2019
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Wellcome Trust, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, National Institute for Health and Care Research, National Institutes of Health, Medical Research Council, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Mechanisms of Zika Virus Maternal-Fetal Transmission, G2204161919, Increasing the flavivirus envelope glycoprotein dimer stability to elicit potent and broadly neutralizing antibody responses, G2644599808, Human neutralizing antibodies for Zika virus, G4336488413, Antibody-based Protection against Flavivirses, G6601593777, Studies of immunopathogenesis in dengue virus infection., G9000003096, G9000256497, Infectious Disease/Basic Microbial Pathogenic Mechanisms, Training Program in Basic Immunology, Protective immunity following dengue virus natural infections and vaccination
OpenAlex ID: W2912383155