Heterosubtypic immunity to influenza mediated by liposome adjuvanted H5N1 recombinant protein vaccines

• Published in: Vaccine Vol. 28; no. 41; pp. 6765 - 6777
• Main Authors: Thueng-in, Kanyarat, Maneewatch, Santi, Srimanote, Potjanee, Songserm, Thaweesak, Tapchaisri, Pramuan, Sookrung, Nitat, Tongtawe, Pongsri, Channarong, Sunee, Chaicumpa, Wanpen
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 24-09-2010; Elsevier; Elsevier Limited
• Subjects: Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Animal models; Animals; Antibodies, Viral - blood; Antibody Formation; Antibody response; Avian flu; Biological and medical sciences; Cholesterol; Cross Protection; Cytokines; Cytokines - immunology; Cytotoxic lymphocytes; Cytotoxicity; Data processing; Deoxyribonucleic acid; DNA; Dogs; Fundamental and applied biological sciences. Psychology; H1N1; H5N1; Helper cells; Heterosubtypic immunity; Histopathology; Immune response; Immunity; Immunization; Immunogenicity; Immunological memory; Infection; Infectivity; Influenza; Influenza A virus; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccine; Influenza Vaccines - immunology; Intramuscular; Lecithin; Liposome; Liposomes; Liposomes - immunology; Lung; Lung - pathology; Lung - virology; Lymphocytes; Lymphocytes T; M2 protein; Mammals; Mice; Mice, Inbred BALB C; Microbiology; Neutralization Tests; Nucleoprotein (NP); Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Pandemics; Plasmids; Proteins; Recombinant Proteins - immunology; RNA-Binding Proteins - immunology; RT-PCR; Side effects; Swine flu; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Viral Core Proteins - immunology; Viral infections; Viral Matrix Proteins - immunology; Virology; Viruses; Immunization; Immune response; Cytokines; M2 protein; Cytotoxic lymphocytes; Liposome; Intramuscular; Nucleoprotein (NP); H1N1; H5N1; Influenza; RT-PCR; Heterosubtypic immunity; Mice; Influenza vaccine; Orthomyxoviridae; Cytotoxicity; Nucleoprotein; Avian influenzavirus; Recombinant protein; Cytotoxic T lymphocyte; Reverse transcription polymerase chain reaction; Rodentia; Cytokine; Zoopathogen; Vaccine; Infection; Virus; Vertebrata; Influenzavirus A; Mammalia; Mouse; Viral disease; Immunological adjuvant; Influenzavirus A(H1N1)
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.07.065

Abstract A non-egg, non-culture based influenza vaccine that intervenes large influenza outbreaks and protects against heterosubtypic infections is needed. Candidates of such vaccine are likely to be conserved influenza virus proteins or their coding DNA. The vaccine must be conveniently produced at reasonable cost, safe, highly immunogenic and should be able to recall rapidly the immunological memory upon the antigenic re-exposure. In this study vaccines made of full length recombinant NP and M2 of the H5N1 influenza A virus were entrapped either alone or together into liposome (L) made of phosphatidylcholine and cholesterol. The vaccines (L-NP, L-M2 or L-NP + M2) and mocks (L or PBS) were safe without causing any adverse reaction in the intramuscularly injected mice. They were readily immunogenic at a single dose and a recalled response could be detected within one day post booster. Cytokine and antibody data indicated that the vaccines induced a Th1 bias immune response. NP containing vaccines stimulated a marked increase of cytotoxic lymphocytes, i.e., CD8+ , intracellular IFNγ+ cells, while M2 containing vaccines elicited good antibody response which neutralized infectivity of heterologous influenza viruses. Although the three vaccines elicited different immunological defense factors; nevertheless, they similarly and readily abrogated lung histopathology mediated by viruses belonging to different H5N1 clade/subclade and heterosubtypes including swine H1N1 and human H1N1/2009 viruses. They protected the vaccinated mice against lethal challenges with mouse adapted avian H5N1 virus. The liposome adjuvanted vaccines which demonstrated high protective efficacy in mice warrant testing further in a non-rodent model as well as in humans.