title: Antibodies targeting dengue virus envelope domain III are not required for serotype-specific protection or prevention of enhancement in vivo.
abstract: The envelope (E) protein of dengue virus (DENV) is composed of three domains (EDI, EDII, EDIII) and is the main target of neutralizing antibodies. Many monoclonal antibodies that bind EDIII strongly neutralize DENV. However in vitro studies indicate that anti-EDIII antibodies contribute little to the neutralizing potency of human DENV-immune serum. In this study, we assess the role of anti-EDIII antibodies in mouse and human DENV-immune serum in neutralizing or enhancing DENV infection in mice. We demonstrate that EDIII-depleted human DENV-immune serum was protective against homologous DENV infection in vivo. Although EDIII-depleted DENV-immune mouse serum demonstrated decreased neutralization potency in vitro, reduced protection in some organs, and enhanced disease in vivo, administration of increased volumes of EDIII-depleted serum abrogated these effects. These data indicate that anti-EDIII antibodies contribute to protection and minimize enhancement when present, but can be replaced by neutralizing antibodies targeting other epitopes on the dengue virion.
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Williams
authors.forename: Wahala M P B
authors.initials: WM
authors.lastname: Wahala
authors.forename: Susana
authors.initials: S
authors.lastname: Orozco
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins