Influenza hemagglutinin peptides fused to interferon gamma and encapsulated in liposomes protects mice against influenza infection.
The immunogenicity of a peptide vaccine may be improved by fusing antigen to a cytokine and administering this chimeric protein in a particulate delivery system. We have investigated this using a vaccine comprising an immunodominant T cell epitope and a B cell epitope from influenza haemagglutinin (HATB) fused to interferon gamma and encapsulated in liposomes (HATB/IFN-gamma/lipo). Controls comprised groups receiving HATB/IFN-gamma mixed with liposomes, HATB incorporated in liposomes or heat inactivated PR8 influenza virus (HI PR8). IFN-gamma production in mice treated with HATB/IFN-gamma/lipo was significantly higher than in mice inoculated with either HATB/IFN-gamma mixed with liposomes or HATB incorporated in liposomes but less than HI PR8. Lung viral titres were significantly lower in mice treated with HATB/IFN-gamma/lipo compared with those treated with HATB/IFN-gamma mixed with liposomes. HI PR8-treated mice recorded a nil viral titre. There was no correlation between the level of antibody production and clearance of virus from the lungs. These data suggest that particulate delivery systems may be useful adjuncts to improve immune responses to chimeric proteins and to induce protection against disease.
Faulkner
L
L
Department of Microbiology, University of Otago, PO Box 56, Dunedin, New Zealand.
Buchan
G
G
Slobbe
L
L
Lockhart
E
E
Wales
J
J
Wilson
M
M
Baird
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D004274:DNA, Recombinant / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016056:Immunodominant Epitopes / Q000235:genetics; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008081:Liposomes; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D000914:Antibodies, Viral; D004274:DNA, Recombinant; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016056:Immunodominant Epitopes; D007252:Influenza Vaccines; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma