Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection
Top Cited Papers
- 19 August 2016
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 353 (6301), 823-826
- https://doi.org/10.1126/science.aaf8505
Abstract
Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV–cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice. Memory T cells against NS1 or E proteins were poorly cross-reactive, even in donors preexposed to DENV. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.Keywords
Funding Information
- European Union (HEALTH-F3-2011-281803-Project IDAMS)
- European Research Council (323183 PREDICT)
- Swiss National Science Foundation (160279)
- U.S. National Institutes of Health (R01 AI24493)
- Ministero della Salute, Fondazione IRCCS Policlinico San Matteo, Ricerca Corrente (8020615)
- Helmut Horten Foundation
This publication has 53 references indexed in Scilit:
- Persistence of Circulating Memory B Cell Clones with Potential for Dengue Virus Disease Enhancement for Decades following InfectionJournal of Virology, 2012
- Analysis of Epitopes on Dengue Virus Envelope Protein Recognized by Monoclonal Antibodies and Polyclonal Human Sera by a High Throughput AssayPLoS Neglected Tropical Diseases, 2012
- High-Resolution Description of Antibody Heavy-Chain Repertoires in HumansPLOS ONE, 2011
- The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing ActivityCell Host & Microbe, 2010
- Human naive and memory CD4+ T cell repertoires specific for naturally processed antigens analyzed using libraries of amplified T cellsThe Journal of Experimental Medicine, 2009
- A Therapeutic Antibody against West Nile Virus Neutralizes Infection by Blocking Fusion within EndosomesPLoS Pathogens, 2009
- Antibodies to Envelope Glycoprotein of Dengue Virus during the Natural Course of Infection Are Predominantly Cross-Reactive and Recognize Epitopes Containing Highly Conserved Residues at the Fusion Loop of Domain IIJournal of Virology, 2008
- IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysisNucleic Acids Research, 2008
- Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloningJournal of Immunological Methods, 2008
- An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirusNature Medicine, 2004