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1762006 
Journal Article 
Delta inulin polysaccharide adjuvant enhances the ability of split-virion H5N1 vaccine to protect against lethal challenge in ferrets 
Layton, RC; Petrovsky, N; Gigliotti, AP; Pollock, Z; Knight, J; Donart, N; Pyles, J; Harrod, KS; Gao, P; Koster, F 
2011 
1 
Vaccine
ISSN: 0264-410X
EISSN: 1873-2518 
29 
37 
6242-6251 
21736913 
WOS:000295243800012 
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 (TM), 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 p,g or 22.5 lig of a split-virion preparation of
A/Vietnam/1203/2004 with or without adjuvant. An additional group received just one immunization
with 22.5 lig 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 EID(50) 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 (TM) adjuvant formulations improved the protective
efficacy of a split-virion H5N1vaccine as measured by significantly enhanced immunogenicity,
survival, and reduced morbidity. (C) 2011 Elsevier Ltd. All rights reserved. 
Influenza; Vaccine; Ferret; Adjuvant