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Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens
Journal article   Open access

Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens

Dominick J Laddy, Jian Yan, Michele Kutzler, Darwyn Kobasa, Gary P Kobinger, Amir S Khan, Jack Greenhouse, Niranjan Y Sardesai, Ruxandra Draghia-Akli and David B Weiner
PloS one, v 3(6), pp e2517-e2517
25 Jun 2008
DOI: https://doi.org/10.1371/journal.pone.0002517
PMID: 18575608
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0002517View
Published, Version of Record (VoR) Open

Abstract

Antibodies, Viral - biosynthesis DNA - immunology Enzyme-Linked Immunosorbent Assay Humans Mice, Inbred C57BL Vaccines, DNA - immunology Electroporation Male Macaca mulatta DNA Primers Ferrets Orthomyxoviridae - immunology Cross Reactions Animals Base Sequence Antibodies, Viral - immunology Antigens - immunology Female Mice Mice, Inbred BALB C
The persistent evolution of highly pathogenic avian influenza (HPAI) highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA), N1 neuraminidase (pN1NA), and nucleoprotein antigen (pNP). Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40) were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the antigenic drift that will likely occur before these viruses cross the species barrier to humans.

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127 citations in Web of Science
132 citations in Scopus

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Collaboration types
Industry collaboration
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
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