Demonstration of d‑Octaarginine-Linked Polymers as Promising Adjuvants for Mucosal Vaccination through Influenza Virus Challenge

Mucosal vaccination is one of the most effective ways to reduce the risk of pandemics as a result of incorrect prediction of epidemic strains of influenza viruses or virus mutation. However, adjuvants and antigen carriers with potent immunostimulatory activities are a prerequisite for significant in...

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Published in:Bioconjugate chemistry 2016-08, Vol.27 (8), p.1865-1871
Main Authors: Miyata, Kohei, Mohri, Kohta, Egawa, Tomomi, Endo, Rikito, Morimoto, Naoki, Ochiai, Kyohei, Hiwatari, Ken-ichiro, Tsubaki, Kazufumi, Tobita, Etsuo, Uto, Tomofumi, Baba, Masanori, Sakuma, Shinji
Format: Article
Language:English
Subjects:
Acrylic Resins - chemistry
Adjuvants, Immunologic - chemistry
Adjuvants, Immunologic - pharmacology
Animals
Antigens
Female
Immunization
Immunoglobulin G - blood
Immunoglobulin G - immunology
Influenza
Influenza A Virus, H1N1 Subtype - immunology
Influenza virus
Mice
Mice, Inbred BALB C
Mucous Membrane - immunology
Mutation
Oligopeptides - chemistry
Oligopeptides - immunology
Polymers
Polymers - chemistry
Vaccination
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Summary:Mucosal vaccination is one of the most effective ways to reduce the risk of pandemics as a result of incorrect prediction of epidemic strains of influenza viruses or virus mutation. However, adjuvants and antigen carriers with potent immunostimulatory activities are a prerequisite for significant induction of mucosal immunity because most antigens are poorly immunogenic when solely applied to the mucosa. Our previous studies demonstrated that poly­(N-vinylacetamide-co-acrylic acid) bearing d-octaarginine induced the secretion of antigen-specific immunoglobulin A (IgA) on the mucosa when nasally administered with virus antigens and that intranasal IgA reacts to viral strains other than the one used for immunization. Therefore, the present study evaluated capabilities of secreted IgA for protection against virus infection. When mice were inoculated with a mixture of inactivated H1N1 A/Puerto Rico/8/34 influenza viruses and d-octaarginine-linked polymers, antigen-specific secreted IgA was induced on the nasal mucosa. Immunized mice were completely protected from virus infection of the inoculated strain. To the contrary, mice nasally inoculated with inactivated viruses alone were infected with the homologous viruses presumably because of insignificant induction of secreted IgA. Results demonstrated that our polymer would be a promising adjuvant for mucosal vaccination.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.6b00283