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ARS Home » Research » Publications at this Location » Publication #125092
Title: HETEROSUBTYPIC IMMUNITY AGAINST HUMAN INFLUENZA A VIRUSES INCLUDING RECENTLY EMERGED AVIAN H5 AND H9 VIRUSES INDUCED BY FLU-ISCOM VACCINE IN MICE REQUIRES BOTH CTL AND MACROPHAGE FUNCTION

Author
item SAMBHARA,, SURYAPRAKASH - AVENTIS PASTEUR CANADA
item KURICHH,, ANJNA - AVENTIS PASTEUR CANADA
item MIRANDA,, RENATA - AVENTIS PASTEUR CANADA
item Tumpey, Terrence
item ROWE,, THOMAS - CDC - ATLANTA, GEORGIA
item RENSHAW,, MARY - CDC - ATLANTA, GEORGIA
item ARPINO,, RITA - AVENTIS PASTEUR CANADA
item TAMANE,, ALAN - AVENTIS PASTEUR CANADA
item KANDIL,, ALI - AVENTIS PASTEUR CANADA
item JAMES,, OLIVE - AVENTIS PASTEUR CANADA

Submitted to: Cellular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/24/2001
Publication Date: 10/31/2001
Citation: N/A

Interpretive Summary: In 1997 in Hong Kong, 18 human cases of respiratory illness were caused by an avian influenza A H5N1 virus. Although avian influenza viruses had not previously been known to cause respiratory illness in humans, the H5N1 viruses caused severe illness and death, primarily in individuals aged >12 years. Since H5N1 viruses were previously isolated only from avian species, their emergence into a largely serologically naive human population raises concerns regarding the pandemic potential of these viruses. In this communication, we demonstrate for the first time that an influenza vaccine (H1N1) formulated as immunostimulating complexes confers significant levels of protection, enhanced recovery and clearance of virus following challenge with a number of strains of viruses (H2N2, H3N2, and H9N2) as well as the highly pathogenic avian H5N1 viruses isolated from humans in 1997 in Hong Kong. Therefore, inactivated influenza vaccine formulated as described could serve as a broadly cross-protective vaccine against pandemic and epidemic influenza.

Technical Abstract: Induction of heterosubtypic immunity to influenza viral antigens is of paramount importance to the prevention of epidemics and potential pandemics. The 1997 incidence of avian influenza infections in humans in Hong Kong heightened the need for pandemic preparedness and search for vaccines and vaccine delivery systems that can confer broad protection. In this report, we demonstrate that the delivery of H1N1 subtype influenza viral antigens as ISCOM induces broad cross protection in mice against challenge with various influenza virus subtypes including the avian H9 and the H5 strain that was recently responsible for deaths in humans. The ISCOM delivery system induced high and long-lived serum antiviral antibodies and class I restricted cytotoxic T-lymphocytes. Studies with gene knock-out mice demonstrated that the heterosubtypic protection required cross-reactive, functional cytotoxic T cells and non hemagglutination inhibiting serum antibodies. H1N1 influenza antigens failed to induce significant CTL or long lasting antibody responses or protect mice against challenge with heterosubtypic viruses. These results suggest that exogenous delivery of influenza antigens as ISCOM can influence their antigen processing and presentation, their ability to induce/recall CTL specificties and their capacity to mediate broad cross-protection against influenza virus variants.