Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses.
Immunization against conserved virus components induces broad, heterosubtypic protection against diverse influenza A viruses, providing a strategy for controlling unexpected outbreaks or pandemics until strain-matched vaccines become available. This study characterized immunization to nucleoprotein (NP) and matrix 2 (M2) by DNA priming followed by parenteral or mucosal boosting in mice and ferrets. DNA vaccination followed by boosting with antigen-matched recombinant adenovirus (rAd) or cold-adapted (ca) influenza virus provided robust protection against virulent H1N1 and H5N1 challenges. Compared to other boosts, mucosal rAd induced stronger IgA responses, more virus-specific activated T-cells in the lung, and better protection against morbidity following challenge even eight months post-boost. In ferrets, both mucosal and parenteral rAd boosting protected from lethal H5N1 challenge. These findings demonstrate potent protection by vaccination highly focused on conserved antigens and identify immune response measures in mice that differed among vaccinations and correlated with outcome.
Price
Graeme E
GE
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
Soboleski
Mark R
MR
Lo
Chia-Yun
CY
Misplon
Julia A
JA
Pappas
Claudia
C
Houser
Katherine V
KV
Tumpey
Terrence M
TM
Epstein
Suzanne L
SL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005289:Ferrets; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000097:blood; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016601:RNA-Binding Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C048842:NP protein, Influenza A virus