title: Protective immunity to H7N9 influenza viruses elicited by synthetic DNA vaccine.
abstract: Despite an intensive vaccine program influenza infections remain a major health problem, due to the viruses' ability to change its envelope glycoprotein hemagglutinin (HA), through shift and drift, permitting influenza to escape protection induced by current vaccines or natural immunity. Recently a new variant, H7N9, has emerged in China causing global concern. First, there have been more than 130 laboratory-confirmed human infections resulting in an alarmingly high death rate (32.3%). Second, genetic changes found in H7N9 appear to be associated with enabling avian influenza viruses to spread more effectively in mammals, thus transmitting infections on a larger scale. Currently, no vaccines or drugs are effectively able to target H7N9. Here, we report the rapid development of a synthetic consensus DNA vaccine (pH7HA) to elicit potent protective immunity against the H7N9 viruses. We show that pH7HA induces broad antibody responses that bind to divergent HAs from multiple new members of the H7N9 family. These antibody responses result in high-titer HAI against H7N9. Simultaneously, this vaccine induces potent polyfunctional effector CD4 and CD8T cell memory responses. Animals vaccinated with pH7HA are completely protected from H7N9 virus infection and any morbidity associated with lethal challenge. This study establishes that this synthetic consensus DNA vaccine represents a new tool for targeting emerging infection, and more importantly, its design, testing and development into seed stock for vaccine production in a few days in the pandemic setting has significant implications for the rapid deployment of vaccines protecting against emerging infectious diseases.
authors.affiliation: Inovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Villarreal
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Winnipeg, Manitoba R2E 3R2, Canada.
authors.forename: Trina
authors.initials: T
authors.lastname: Racine
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jaemi S
authors.initials: JS
authors.lastname: Chu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jewell N
authors.initials: JN
authors.lastname: Walters
authors.affiliation: Inovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Morrow
authors.affiliation: Inovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Inovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Inovio Pharmaceuticals, Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA.
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Winnipeg, Manitoba R2E 3R2, Canada.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dbweiner@mail.med.upenn.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000918:Antibody Specificity; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007111:Immunity, Cellular; D007156:Immunologic Memory; D064766:Influenza A Virus, H7N9 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic
keywords: DNA vaccine; H7N9; Hemagglutinin (HA)