Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. III. Delivery of recombinant nucleoprotein to the immune system using attenuated Salmonella typhimurium as a live carrier.
A plasmid encoding the influenza nucleoprotein gene from A/NT/60/68 virus was transduced into the attenuated Salmonella typhimurium aroA- strain SL3261. The bacterial vector expressing the viral gene product was able to induce both humoral and cell-mediated immune responses to the nucleoprotein antigen. CD4+ virus-specific T cells capable of proliferation were readily induced and, in some circumstances, class II major histocompatibility complex (MHC)-restricted cytotoxicity was detected. However, virus-specific class I MHC-restricted cytotoxic T lymphocytes (CTL) were not detected after such immunization. Mice immunized orally with the nucleoprotein-expressing bacteria mounted a strong anti-viral antibody response and spleen cells from such mice proliferated specifically to virus challenge in vitro, producing interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). Orally immunized mice showed significant protection from challenge infection with influenza virus if the mice were also boosted intranasally before infection.
Tite
J P
JP
Department of Experimental Immunobiology, Wellcome Biotech, Beckenham, Kent, U.K.
Gao
X M
XM
Hughes-Jenkins
C M
CM
Lipscombe
M
M
O'Callaghan
D
D
Dougan
G
G
Liew
F Y
FY
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D005822:Genetic Vectors; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009698:Nucleoproteins / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010957:Plasmids; D011994:Recombinant Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D009698:Nucleoproteins; D011994:Recombinant Proteins