Abstract
The development of an anti-influenza vaccine with the potential for cross-protection against seasonal drift variants as well as occasionally emerging reassortant viruses is essential. In this study, we successfully generated a novel anti-influenza vaccine system combining conserved matrix protein 2 (sM2) and stalk domain of hemagglutinin (HA2) fusion protein (sM2HA2) and poly-γ-glutamic acid (γ-PGA)-based vaccine adjuvant systems that can act as a mucoadhesive delivery vehicle of sM2HA2 as well as a robust strategy for the incorporation of hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21. Intranasal coadministration of sM2HA2 and the combination adjuvant γ-PGA/MPL/QS21 (CA-PMQ) was able to induce a high degree of protective mucosal, systemic, and cell-mediated immune responses. The sM2HA2/CA-PMQ immunization was able to prevent disease symptoms, confering complete protection against lethal infection with divergent influenza subtypes (H5N1, H1N1, H5N2, H7N3, and H9N2) that lasted for at least 6 mo. Therefore, our data suggest that mucosal administration of sM2HA2 in combination with CA-PMQ could be a potent strategy for a broad cross-protective influenza vaccine, and CA-PMQ as a mucosal adjuvant could be used for effective mucosal vaccines.
Copyright © 2015 by The American Association of Immunologists, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / chemistry*
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Animals
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Cross Protection / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / chemistry
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Host-Pathogen Interactions / immunology
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Immune System / immunology
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Immunity, Cellular / immunology
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Immunity, Mucosal / immunology
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Immunization
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Influenza A Virus, H1N1 Subtype / immunology
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Influenza A Virus, H1N1 Subtype / physiology
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Influenza A Virus, H5N1 Subtype / immunology
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Influenza A Virus, H5N1 Subtype / physiology
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Influenza A Virus, H5N2 Subtype / immunology
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Influenza A Virus, H5N2 Subtype / physiology
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Influenza A Virus, H7N3 Subtype / immunology
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Influenza A Virus, H7N3 Subtype / physiology
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Influenza A Virus, H9N2 Subtype / immunology
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Influenza A Virus, H9N2 Subtype / physiology
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Influenza Vaccines / administration & dosage
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Influenza Vaccines / chemistry*
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Influenza Vaccines / immunology*
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Mice, Inbred BALB C
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control
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Orthomyxoviridae Infections / virology
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Polyglutamic Acid / analogs & derivatives
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Polyglutamic Acid / chemistry
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Polyglutamic Acid / immunology
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Polymers / chemistry*
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Viral Matrix Proteins / chemistry
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Viral Matrix Proteins / immunology
Substances
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Adjuvants, Immunologic
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Hemagglutinin Glycoproteins, Influenza Virus
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Influenza Vaccines
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M2 protein, Influenza A virus
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Polymers
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Viral Matrix Proteins
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poly(gamma-glutamic acid)
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Polyglutamic Acid