Mannan adjuvants intranasally administered inactivated influenza virus in mice rendering low doses inductive of strong serum IgG and IgA in the lung

BMC Infectious Diseases

Geoffrey Pietersz⁴  Ian Barr¹  Karen Laurie¹  Choon-Kit Tang³  Sandra Esparon²  Owen Proudfoot² 

[1] WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn Street North, Melbourne 3051, Australia;Bio-organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, 85 Commercial Road, Melbourne 3004, Australia;Immunology Frontier Research Centre, 6F IFReC Research Building, 3-1 Yamada-oka, Suita, Osaka, Japan;Department of Immunology, Monash University, Melbourne, Victoria, Australia

关键词: Vaccine;    Mucosal immunity;    Mannan;    Intranasal;    Immunisation;    Influenza;    IgA;    H1N1;    Dose-sparing;    Adjuvant;   

Others  :  1135689
DOI  :  10.1186/s12879-015-0838-7

 received in 2014-08-21, accepted in 2015-02-13,  发布年份 2015

【 摘 要 】

Background

H1N1 influenza viruses mutate rapidly, rendering vaccines developed in any given year relatively ineffective in subsequent years. Thus it is necessary to generate new vaccines every year, but this is time-consuming and resource-intensive. Should a highly virulent influenza strain capable of human-to-human transmission emerge, these factors will severely limit the number of people that can be effectively immunised against that strain in time to prevent a pandemic. An adjuvant and mode of administration capable of rendering ordinarily unprotective vaccine doses protective would thus be highly advantageous.

Methods

The carbohydrate mannan was conjugated to whole inactivated H1N1 influenza virus at a range of ratios, and mixed with it at a range of ratios, and various doses of the resulting preparations were administered to mice via the intranasal (IN) route. Serum immunity was assessed via antigen-specific IgG ELISA and the haemagglutination-inhibition (HI) assay, and mucosal immunity was assessed via IgA ELISA of bronchio-alveolar lavages.

Results

IN-administered inactivated H1N1 mixed with mannan induced higher serum IgG and respiratory-tract IgA than inactivated H1N1 conjugated to mannan, and HIN1 alone. Adjuvantation was mannan-dose-dependent, with 100 μg of mannan adjuvanting 1 μg of H1N1 more effectively than 10 or 50 μg of mannan. Serum samples from mice immunised with 1 μg H1N1 adjuvanted with 10 μg mannan did not inhibit agglutination of red blood cells (RBCs) at a dilution factor of 10 in the HI assay, but samples resulting from adjuvantation with 50 and 100 μg mannan inhibited agglutination at dilution factors of ≥ 40. Both serum IgG₁ and IgG_2a were induced by IN mannan-adjuvanted H1N1 vaccination, suggesting the induction of humoral and cellular immunity.

Conclusions

Mixing 100 μg of mannan with 1 μg of inactivated H1N1 adjuvanted the vaccine in mice, such that IN immunisation induced higher serum IgG and respiratory tract IgA than immunisation with virus alone. The serum from mice thus immunised inhibited H1N1-mediated RBC agglutination strongly in vitro. If mannan similarly adjuvants low doses of influenza vaccine in humans, it could potentially be used for vaccine ‘dose-sparing’ in the event that a vaccine shortage arises from an epidemic involving a highly virulent human-to-human transmissable influenza strain.

【 授权许可】

   
2015 Proudfoot et al.; licensee BioMed Central.

【 图 表 】

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