Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection

Asahi-Ozaki, Yasuko; Itamura, Shigeyuki; Ichinohe, Takeshi; Strong, Peter; Tamura, Shinichi; Takahashi, Hitomi; Sawa, Hirofumi; Moriyama, Masami; Tashiro, Masato; Sata, Tetsutaro; Kurata, Takeshi; Hasegawa, Hideki

doi:10.1016/j.micinf.2006.07.018

Cited by 52 publications

(27 citation statements)

References 30 publications

(43 reference statements)

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“…These findings were consistent with results showing the protective effects against avirulent influenza virus (A/ PR8, H1N1) infection in mice by intranasal administration of chitin microparticles into the lung (unpublished data by P. Strong). It is previously reported that chitin microparticles had a mucosal adjuvant effect when coadministered with an influenza hemagglutinin vaccine and increased both the mucosal and systemic humoral responses that provided complete protection against challenge with the homologous influenza virus H1N1 or H5N1 in mice Asahi-Ozaki et al, 2006;Ichinohe et al, 2006]. The current study demonstrates hitherto unrecognized effects of chitin microparticles in enhancing innate protection against infection with a highly pathogenic avian influenza virus strain.…”

Section: Discussionsupporting

confidence: 53%

Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus

Ichinohe

Nagata

Strong³

et al. 2007

Journal of Medical Virology

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Highly pathogenic avian influenza virus (H5N1) is an emerging pathogen with the potential to cause great harm to humans, and there is concern about the potential for a new influenza pandemic. This virus is resistant to the antiviral effects of interferons and tumor necrosis factor-alpha. However, the mechanism of interferon-independent protective innate immunity is not well understood. The prophylactic effects of chitin microparticles as a stimulator of innate mucosal immunity against a recently obtained strain of H5N1 influenza virus infection were examined in mice. Clinical parameters and the survival rate of mice treated by intranasal application of chitin microparticles were significantly improved compared to non-treated mice after a lethal influenza virus challenge. Flow cytometric analysis revealed that the number of natural killer cells that expressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and that had migrated into the cervical lymph node was markedly increased (26-fold) after intranasal treatment with chitin microparticles. In addition, the level of IL-6 and interferon-gamma-inducible protein-10 (IP-10) in the nasal mucosa after H5N1 influenza virus challenge was decreased by prophylactic treatment with chitin microparticles. These results suggest that prophylactic intranasal administration of chitin microparticles enhanced the local accumulation of natural killer cells and suppressed hyper-induction of cytokines, resulting in an innate immune response to prevent pathogenesis of H5N1 influenza virus.

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Section: Discussionsupporting

confidence: 53%

Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus

Ichinohe

Nagata

Strong³

et al. 2007

Journal of Medical Virology

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“…After fixation, the tissues were embedded in paraffin by conventional methods and stained with hematoxylin and eosin (H&E), or subjected to immunohistochemical staining with antiserum against the nucleoprotein from the influenza A/PR8 virus. The specificity of the anti-nucleoprotein Ab and its reactivity to influenza A H5N1 influenza virus have been confirmed previously [Nishimura et al, 2000;Asahi-Ozaki et al, 2006]. Immunohistochemical staining was performed by the biotin-streptavidin-peroxidase method using 3,3 0 -diaminobenzidine as a substrate.…”

Section: Histopathological and Immunohistochemical Analysesmentioning

confidence: 73%

Intranasal administration of adjuvant‐combined vaccine protects monkeys from challenge with the highly pathogenic influenza A H5N1 virus

Ichinohe

Ainai

Ami

et al. 2010

Journal of Medical Virology

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The effectiveness in cynomolgus macaques of intranasal administration of an influenza A H5N1 pre-pandemic vaccine combined with synthetic double-stranded RNA (polyI/polyC12U) as an adjuvant was examined. The monkeys were immunized with the adjuvant-combined vaccine on weeks 0, 3, and 5, and challenged with the homologous virus 2 weeks after the third immunization. After the second immunization, the immunization induced vaccine-specific salivary IgA and serum IgG antibodies, as detected by ELISA. The serum IgG antibodies present 2 weeks after the third immunization not only had high neutralizing activity against the homologous virus, they also neutralized significantly heterologous influenza A H5N1 viruses. The vaccinated animals were protected completely from the challenge infection with the homologous virus. These results suggest that intranasal immunization with the Double stranded RNA-combined influenza A H5N1 vaccine induce mucosal IgA and serum IgG antibodies which could protect humans from homologous influenza A H5N1 viruses which have a pandemic potential.

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“…It has been reported that poly(I·C) mimics an influenza virus infection because the same double-stranded RNA (dsRNA) is produced during viral RNA replication (2,19,41). Other investigators have reported that dsRNA also activates PKA to phosphorylate CREB (25,26), which is necessary for it to bind the COX2 promoter (35).…”

Section: Production Of Ifn-1 Is Enhanced By Cox2 During Influenza Virmentioning

confidence: 99%

Epigenetic Changes Mediated by MicroRNA miR29 Activate Cyclooxygenase 2 and Lambda-1 Interferon Production during Viral Infection

Fang

Hao

Liu

et al. 2012

J Virol

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Lambda-1 interferon (IFN-1) and cyclooxygenase-2 (COX-2) were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-1 and COX2 are activated and modulated during viral infection remains unclear. In this study, we found that expression of both circulating IFN-1 and COX2-derived prostaglandin E2 (PGE2) was coordinately elevated in a cohort of influenza patients compared to healthy individuals. Expression of IFN-1 was blocked by a selective COX2 inhibitor during influenza A virus infection in A549 human lung epithelial cells but enhanced by overexpression of COX2, indicating that the production of IFN-1 is COX2 dependent. COX2 was able to increase IFN-1 expression by promoting NF-B binding to the enhancer in the IFN-1 promoter. We found that epigenetic changes activate COX2 expression and PGE2 accumulation during viral infection. The expression of DNA methyltransferase 3a (DNMT3a) and DNMT3b, but not that of DNMT1, was downregulated following influenza A virus infection in both A549 cells and peripheral blood mononuclear cells (PBMCs). We showed that microRNA miR29 suppresses DNMT activity and thus induces expression of COX2 and PGE2. Furthermore, miR29 expression was elevated 50-fold in virally infected A549 cells and 10-fold in PBMCs from influenza patients, compared to expression after mock infection of A549 cells or in healthy individuals, respectively. Activation of the protein kinase A signaling pathway and phosphorylation of CREB1 also contributed to COX2 expression. Collectively, our work defines a novel proinflammatory cascade in the control of influenza A virus infection.

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Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection

Cited by 52 publications

References 30 publications

Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus

Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus

Intranasal administration of adjuvant‐combined vaccine protects monkeys from challenge with the highly pathogenic influenza A H5N1 virus

Epigenetic Changes Mediated by MicroRNA miR29 Activate Cyclooxygenase 2 and Lambda-1 Interferon Production during Viral Infection

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