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Published Online: 20 September 2018

A Synthetic Micro-Consensus DNA Vaccine Generates Comprehensive Influenza A H3N2 Immunity and Protects Mice Against Lethal Challenge by Multiple H3N2 Viruses

Publication: Human Gene Therapy
Volume 29, Issue Number 9

Abstract

Influenza A H3N2 viruses circulate globally, leading to substantial morbidity and mortality. Commercially available, antigen-matched influenza vaccines must be updated frequently to match dynamic sequence variability in immune epitopes, especially within viral influenza A H3N2 hemagglutinin (H3). In an effort to create comprehensive immune responses against H3N2, four micro-consensus antigens were designed to mimic the sequence and antigenic diversity of H3. Synthetic plasmid DNA constructs were developed to express each micro-consensus immunogen and combined into a multi-antigen DNA vaccine cocktail, pH3HA. Facilitated delivery of pH3HA via intramuscular electroporation in mice induced comprehensive, potent humoral responses against diverse seasonal H3N2 viruses that circulated between 1968 and the present. Vaccination with pH3HA also induced an antigen-specific cellular cytokine response. Mice immunized with pH3HA were protected against lethal challenge using two distinct H3N2 viruses, highlighting the heterologous protection afforded by synthetic micro-consensus immunogens. These findings warrant further study of the DNA vaccine micro-consensus platform for broad protection against influenza viruses.

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Information & Authors

Information

Published In

cover image Human Gene Therapy
Human Gene Therapy
Volume 29Issue Number 9September 2018
Pages: 1044 - 1055
PubMed: 30062926

History

Published online: 20 September 2018
Published in print: September 2018
Published ahead of production: 31 July 2018
Accepted: 26 July 2018
Received: 19 May 2018

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Authors

Affiliations

Sarah T.C. Elliott
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
Amelia A. Keaton
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
Jacqueline D. Chu
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
Charles C. Reed
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
Bradley Garman
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
Ami Patel
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
Jian Yan
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
Kate E. Broderick
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
David B. Weiner*
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.

Notes

*
Correspondence: Dr. David B. Weiner, The Wistar Institute of Anatomy and Biology, 3601 Spruce Street, Philadelphia, PA, 19104. [email protected]

Author Disclosure

K.B., J.Y., C.R., and B.G. are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. D.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board services. Remuneration received by D.W. includes direct payments or stock or stock options, and in the interest of disclosure, he notes potential conflicts associated with this work with Inovio and possibly others. In addition, he has a patent DNA vaccine delivery pending to Inovio.

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