Delta inulin polysaccharide adjuvant enhances the ability of split-virion H5N1 vaccine to protect against lethal challenge in ferrets

Abstract Background The reduced immunogenicity of the H5 hemagglutinin (HA), compared to seasonal HA serotypes, has stimulated searches for effective adjuvants to improve H5 vaccine efficacy. This study examined the immunogenicity and protective efficacy in ferrets immunized with a split-virion H5N1...

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Published in:Vaccine 2011-08, Vol.29 (37), p.6242-6251
Main Authors: Layton, R. Colby, Petrovsky, Nikolai, Gigliotti, Andrew P, Pollock, Zemmie, Knight, Jennifer, Donart, Nathaniel, Pyles, John, Harrod, Kevin S, Gao, Peng, Koster, Frederick
Format: Article
Language:English
Subjects:
Adjuvant
Adjuvants
Adjuvants, Immunologic - administration & dosage
Allergy and Immunology
Animal populations
Animals
Antibodies
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
antigens
Applied microbiology
Avian flu
Biological and medical sciences
blood serum
Brain
cell-mediated immunity
Combined vaccines
Disease control
Eggs
Ferret
ferrets
Ferrets - immunology
Fever
Fundamental and applied biological sciences. Psychology
hemagglutination
Hemagglutination inhibition
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinins
histopathology
Immunity (cell-mediated)
Immunization
Immunization, Secondary
Immunogenicity
Influenza
Influenza A virus
Influenza A Virus, H5N1 Subtype - immunology
Influenza Vaccines - administration & dosage
Influenza Vaccines - immunology
Inulin
Inulin - immunology
Laboratory animals
Microbiology
Miscellaneous
Morbidity
Mortality
Mustela
neutralization
neutralizing antibodies
Nose
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - mortality
Polysaccharides
Serotypes
Survival
Temperature effects
Thrombocytopenia
Vaccination
Vaccine
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Viral Load
Virology
weight loss
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Summary:Abstract Background The reduced immunogenicity of the H5 hemagglutinin (HA), compared to seasonal HA serotypes, has stimulated searches for effective adjuvants to improve H5 vaccine efficacy. This study examined the immunogenicity and protective efficacy in ferrets immunized with a split-virion H5N1 vaccine combined with Advax™, a novel delta inulin-based polysaccharide adjuvant technology that has previously demonstrated ability to augment humoral and cellular immunity to co-administered antigens. Methods Ferrets were vaccinated twice 21 days apart with 7.5 μg or 22.5 μg of a split-virion preparation of A/Vietnam/1203/2004 with or without adjuvant. An additional group received just one immunization with 22.5 μg HA plus adjuvant. Serum antibodies were measured by hemagglutination inhibition and microneutralization assays. Vaccinated animals were challenged intranasally 21 days after the last immunization with 106 EID50 of the homologous strain. Morbidity was assessed by observed behavior, weight loss, temperature, cytopenias, histopathology, and viral load. Results No serum neutralization antibody was detected after two immunizations with unadjuvanted vaccine. Two immunizations with high or low dose adjuvanted vaccine stimulated high neutralizing antibody titers. Survival was 100% in all groups receiving adjuvanted-vaccine including the single dose group, compared to 67% survival with unadjuvanted vaccine, and 0% survival in saline or adjuvant-alone controls. Minimal morbidity was seen in all animals receiving adjuvanted vaccine, and was limited to rhinorrhea and mild thrombocytopenia, without fever, weight loss, or reduced activity. H5N1 virus was cleared from the nasal wash by day 4 post-challenge only in animals receiving adjuvanted vaccine which also prevented viral invasion of the brain in most animals. Conclusions In this initial study, Advax™ adjuvant formulations improved the protective efficacy of a split-virion H5N1vaccine as measured by significantly enhanced immunogenicity, survival, and reduced morbidity.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2011.06.078