Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein.
Influenza epidemic and pandemic strains cannot be predicted with certainty. Current vaccines elicit antibodies effective against specific strains, but new strategies are urgently needed for protection against unexpected strains. DNA vaccines encoding conserved antigens protect animals against diverse subtypes, but their potency needs improvement. We tested DNA prime-recombinant adenoviral boost immunization to nucleoprotein (NP). Strong antibody and T cell responses were induced. Protection against challenge was T cell-dependent and substantially more potent than DNA vaccination alone. Importantly, vaccination protected against lethal challenge with highly pathogenic H5N1 virus. Thus, gene-based vaccination with NP may contribute to protective immunity against diverse influenza viruses through its ability to stimulate cellular immunity.
Epstein
Suzanne L
SL
Laboratory of Immunology and Developmental Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Bethesda, MD 20852, USA. epsteins@cber.fda.gov
Kong
Wing-pui
WP
Misplon
Julia A
JA
Lo
Chia-Yun
CY
Tumpey
Terrence M
TM
Xu
Ling
L
Nabel
Gary J
GJ
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D017124:Conserved Sequence; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007115:Immunization Schedule; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000235:genetics* / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D009698:Nucleoproteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic