title: Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation.
abstract: Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Eun
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Geza
authors.initials: G
authors.lastname: Erdos
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kenniston
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Louis D
authors.initials: LD
authors.lastname: Falo
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: gambottoa@upmc.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gambotto
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007114:Immunization; D051379:Mice; D022223:Vaccines, Subunit / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000071244:Zika Virus / Q000235:genetics / Q000276:immunology*; D000071243:Zika Virus Infection / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D000914:Antibodies, Viral; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014765:Viral Vaccines
keywords: Adenovirus; Microneedles; Vaccine; ZIKV-E; Zika virus