Studies on cross-reactive antibodies to multiple subtypes of influenza virus henagglutinin induced by mucosal immunization

• Project/Area Number: 21390134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: TAKADA Ayato 北海道大学, 人獣共通感染症リサーチセンター, 教授 (10292062)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Yasuhiko 北海道大学, 人獣共通感染症リサーチセンター, 教授 (90206540) ; ITO Kimihito 北海道大学, 人獣共通感染症リサーチセンター, 教授 (60396314)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 感染防御 / ワクチン / インフルエンザ / 抗体 / 粘膜免疫 / 交差感染防御

Research Abstract

Currently used parenteral influenza vaccines induce serum IgG antibody response against hemagglutinin (HA), but do not protect primary infection in the respiratory tissues. In addition, vaccine-induced antibodies are not cross-reactive to viruses with different HA subtypes from that of vaccine strains. In this study, we found that intranasal immunization of mice with inactivated influenza viruses induced antibodies cross-reactive to multiple HA subtypes. Furthermore, it was suggested that IgA antibodies associated with mucosal immunity played an important role in heterosubtypic inhibition of virus replication.

Research Products

• [Journal Article] Protective efficacy of neutralizing monoclonal antibodies in a nonhumar primate model of ebola hemorrhagic Fever (2012)
  • Author(s): Marzi A, Yoshida R, Miyamoto H, Ishijima M, Suzuki Y, Higuchi M, Matsuyama Y, Igarashi M, Nakayama E, Kuroda M, Saijo M, Feldmann F, Brining D, Feldmann H, Takada A
  • Journal Title: PLoS One Volume: 7(4) Issue: 4 Pages: e36192-e36192
  • DOI: 10.1371/journal.pone.0036192
  • Peer Reviewed
• [Journal Article] Adaptation of a duck influenza A virus in quail (2011)
  • Author(s): Yamada S, Shinya K, Takada A, Ito T, Suzuki T, Suzuki Y, Le QM, Ebina M, Kasai N, Kida H, Horimoto T, Rivailler P, Chen LM, Donis RO, Kawaoka Y
  • Journal Title: J Virol Volume: 86(3) Issue: 3 Pages: 1411-1420
  • DOI: 10.1128/jvi.06100-11
  • Peer Reviewed
• [Journal Article] Gnarled-trunk evolutionary model of influenza A virus hemagglutinin (2011)
  • Author(s): Ito K, Igarashi M, Miyazaki Y, Murakami T, Iida S, Kida H, Takada A
  • Journal Title: PLoS ONE Volume: 6(10) Issue: 10 Pages: e25953-e25953
  • DOI: 10.1371/journal.pone.0025953
  • NAID: 120005476103
  • Peer Reviewed
• [Journal Article] Cross-protective peptide vaccine against influenza A viruses developed in HLA-A*2402 human immunity model (2011)
  • Author(s): Ichihashi T, Yoshida R, Sugimoto C, Takada A, Kajino K
  • Journal Title: PLoS ONE Volume: 6(9) Issue: 9 Pages: e24626-e24626
  • DOI: 10.1371/journal.pone.0024626
  • Peer Reviewed
• [Journal Article] A vaccine prepared from a non-pathogenic H5N1 influenza virus strain from the influenza virus library conferred protective immunity to chickens against the challenge with antigenically drifted highly pathogenic avian influenza virus (2011)
  • Author(s): Samad RA, Nomura N, Tsuda Y, Manzoor R, Kajihara M, Tomabechi D, Sasaki T, Kokumai N, Ohgitani T, Okamatsu M, Takada A, Sakoda Y, Kida H
  • Journal Title: Jpn J Vet Res Volume: 59 (1) Pages: 23-29
  • NAID: 120002777848
• [Journal Article] An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration (2011)
  • Author(s): Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori 0, Manzoor R, Nakayama E, Igarashi M, Tomabechi D, Yoshida R, Okamatsu M, Sakoda Y, Ito K, Kida H, Takada A
  • Journal Title: Jpn J Vet Res Volume: 59(2 & 3) Pages: 89-100
  • NAID: 120003354967
• [Journal Article] Requirement of Siva-1 for replication of influenza A virus through apoptosis induction (2011)
  • Author(s): Shiozaki T, Iwai A, Kawaoka Y, Takada A, Kida H, Miyazaki T
  • Journal Title: J Gen Virol Volume: 92(Pt2) Issue: 2 Pages: 315-325
  • DOI: 10.1099/vir.0.028316-0
• [Journal Article] Characterization of influenza A viruses isolated from wild waterfowls in Zambia (2011)
  • Author(s): Simulundu E, et al
  • Journal Title: J.Gen.Virol. Volume: 92 Issue: 6 Pages: 1416-1427
  • DOI: 10.1099/vir.0.030403-0
  • Peer Reviewed
• [Journal Article] Genetic characterization and susceptibility on poultry and mammal of H7N6 subtype avian influenza virus isolated in Japan in 2009. (2011)
  • Author(s): Uchida Y, Kanehira K, Mase M, Takemae N, Watanabe C, Usui T, Fujimoto Y, Ito T, Igarashi M, Ito K, Takada A, Sakoda Y, Okamatsu M, Yamamoto Y, Nakamura K, Kida H, Hiromoto Y, Tsuda T, Saito T
  • Journal Title: Vet Microbiol Volume: 147(1-2) Issue: 1-2 Pages: 1-10
  • DOI: 10.1016/j.vetmic.2010.05.037
• [Journal Article] Characterization of human single-chain antibodies against highly pathogenic avian influenza H5N1 viruses : mimotope and neutralizing activity (2010)
  • Author(s): Yang, J., Yoshida, R., Kariya, Y., Zhang, X., Hashiguchi, S., Nakashima, T., Suda, Y., Takada, A., Ito, Y., Sugimura, K.
  • Journal Title: Journal of biochemistry Volume: 148 Pages: 507-515
  • DOI: 10.1093/jb/mvq084
  • NAID: 10027879101
  • Peer Reviewed
• [Journal Article] Influenza A virus polymerase inhibits type I interferon inductionby binding to interferon {beta} promoter stimulator 1. (2010)
  • Author(s): Iwai A, Shiozaki T, Kawai T, Akira S, Kawaoka Y, Takada A, Kida H, Miyazaki T
  • Journal Title: J Biol Chem Volume: 285(42) Issue: 42 Pages: 32064-32074
  • DOI: 10.1074/jbc.m110.112458
• [Journal Article] Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory (2010)
  • Author(s): Sakoda Y, Sugar S, Batchluun D, Erdene-Ochir TO, Okamatsu M, Isoda N, Soda K, Takakuwa H, Tsuda Y, Yamamoto N, Kishida N, Matsuno K, Nakayama E, Kajihara M, Yokoyama A, Takada A Sodnomdarjaa R, Kida H
  • Journal Title: Virology Volume: 406(1) Pages: 88-94
• [Journal Article] Antigenic, genetic, and pathogenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from dead whooper swans (Cygnus cygnus) found in northern Japan in 2008 (2010)
  • Author(s): Okamatsu M, Tanaka T, Yamamoto N, Sakoda Y, Sasaki T, Tsuda Y, Isoda N, Kokumai N, Takada A, Umemura T, Kida H
  • Journal Title: Virus Genes Volume: 41(3) Issue: 3 Pages: 351-357
  • DOI: 10.1007/s11262-010-0530-3
• [Journal Article] Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin (2010)
  • Author(s): Igarashi M, Ito K, Yoshida R, Tomabechi D, Kida H, Takada A
  • Journal Title: PLoS ONE Volume: 5(1) Issue: 1 Pages: e8553-e8553
  • DOI: 10.1371/journal.pone.0008553
  • NAID: 120001804925
• [Journal Article] Antigenic, genetic, and pathogenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from dead whooper swans (Cygnus cygnus) found in northern Japan in 2008 (2010)
  • Author(s): Okamatsu M, et al.
  • Journal Title: Virus Genes Volume: 41 Pages: 351-357
  • Peer Reviewed
• [Journal Article] Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratorywaterfowl in Mongolia on the way back from the southern Asia to their northern territory. (2010)
  • Author(s): Sakoda Y, et al.
  • Journal Title: Virology Volume: 406 Pages: 88-94
  • Peer Reviewed
• [Journal Article] Characterization of human single-chain antibodies against highly pathogenic avian influenza H5N1 viruses : Mimotope and neutralizing activity (2010)
  • Author(s): Yang J, et al.
  • Journal Title: J Biochem Volume: 148 Pages: 507-515
  • Peer Reviewed
• [Journal Article] Predicting the Antigenic Structure of the Pandemic(H1N1)2009 Influenza Virus Hemagglutinin. (2010)
  • Author(s): Igarashi, M., Ito, K., Yoshida, R., Tomabechi, D., Kida, H., Takada, A.
  • Journal Title: PLoS ONE 5
  • NAID: 120001804925
  • Peer Reviewed
• [Journal Article] Characterization of H3N6 avian influenza virus isolated from a wild white pelican in Zambia (2009)
  • Author(s): Simulundu E, Mweene A, Tomabechi D, Hang' ombe B, Ishii A, Suzuki Y, Nakamura I, Sawa H, Sugimoto C, Ito K, Kida H, Saiwana L, Takada A
  • Journal Title: Arch Virol Volume: 154(9) Issue: 9 Pages: 1517-1522
  • DOI: 10.1007/s00705-009-0467-9
  • NAID: 120002383247
• [Journal Article] Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutin of influenza A viruses (2009)
  • Author(s): Yoshida R, Igarashi M, Ozaki H, Kishida N, Tomabechi D, Kida H, Ito K, Takada A
  • Journal Title: PLoS Pathog Volume: 5(3) Issue: 3 Pages: e1000350-e1000350
  • DOI: 10.1371/journal.ppat.1000350
• [Journal Article] Characterization of H3N6 avian influenza virus isolated from a wild white pelican in Zambia. (2009)
  • Author(s): Simulundu, E., Mweene, A., Tomabechi, D., Hang'ombe, B., Ishii, A., Suzuki, Y., Nakamura, I., Sawa, H., Sugimoto, C., Ito, K., Kida, H., Saiwana, L., Takada, A.
  • Journal Title: Arch.Virol. 154 Pages: 1517-1522
  • NAID: 120002383247
  • Peer Reviewed
• [Presentation] ウイルス感染と粘膜免疫 (2012)
  • Author(s): 高田礼人
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] ウイルス感染と粘膜免疫 (2012)
  • Author(s): 高田礼人
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌市)(招待講演)
  • Year and Date: 2012-03-31
• [Presentation] Characterization of monoclonal antibodies against the 2009 pandemic H1N1 Influenza virus hemagglutinin (2011)
  • Author(s): Yoshida R, Tomabechi D, Igarashi M, Miyamoto H, Yokoyama A, Kase T, Kida H, Takada A
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-15
• [Presentation] Characterization of monoclonal antibodies against the 2009 pandemic H1N1 influenza virus hemagglutinin (2011)
  • Author(s): Yoshida R, et al
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2011-09-15
• [Presentation] A highly pathogenic avian influenza virus (H5N1) that invaded Japan through waterfowl migration (2011)
  • Author(s): Ka jihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R,Igarashi M, Okamatsu M, Sakoda Y, Kida H, Takada A
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-14
• [Presentation] A highly pathogenic avian influenza virus (H5N1) that invaded Japan through waterfowl migration (2011)
  • Author(s): Kajihara M, et al
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2011-09-14
• [Presentation] パンデミックインフルエンザAウイルス(HIN1)ヘマグルチニンに対するモノクローナル抗体の性状解析 (2010)
  • Author(s): 吉田玲子,苫米地大輔,五十嵐学,宮本洋子,加瀬哲男,喜田宏,高田礼人
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] H3N2インフルエンザウイルスHAに付加された糖鎖は周辺エピトープを覆い隠していたか?～糖鎖付加部位周辺アミノ酸残基の多様性変化の解析～ (2010)
  • Author(s): 五十嵐学,高田礼人,喜田宏,伊藤公人
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] ウイルスの病原性と宿主域-人獣共通感染症としてのインフルエンザ- (2010)
  • Author(s): 高田礼人
  • Organizer: 第75回日本民族衛生学会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-09-25
• [Presentation] ウイルスの病原性と宿主域-人獣共通感染症としてのインフルエンザ- (2010)
  • Author(s): 高田礼人
  • Organizer: 第75回日本民族衛生学会
  • Place of Presentation: 北海道大学(札幌市) 招待講演
  • Year and Date: 2010-09-25
• [Presentation] Prediction of antigenic structure of hemagglutinin of pandemic (H1N1) 2009 influenza virus (2010)
  • Author(s): Igarashi M, Ito K, Kida H, Takada A
  • Organizer: International Conference on Negative Strand Viruses
  • Place of Presentation: Brugge
  • Year and Date: 2010-06-21
• [Presentation] ホモロジーモデリング法による新型HINIインフルエンザウイルスのヘマグルチニンの抗原構造の解析 (2009)
  • Author(s): 五十嵐学,伊藤公人,吉田玲子,喜田宏,高田礼人
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-10-26
• [Presentation] 愛知県でウズラから分離されたH7N6亜型鳥インフルエンザウイルスの遺伝子解析 (2009)
  • Author(s): 内田裕子,真瀬昌司,竹前喜洋,廣本靖明,五十嵐学,伊藤公人,高田礼人,西藤岳彦,津田知幸,山口成夫
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-10-26
• [Presentation] インフルエンザウイルスのヘマグルチニンのMDS解析と変異予測への応用 (2009)
  • Author(s): 伊藤公人,五十嵐学,村上悌治,喜田宏,高田礼人
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-10-26
• [Presentation] 人獣共通感染症としてのインフルエンザ (2009)
  • Author(s): 高田礼人
  • Organizer: 第47回全国大学保健管理研究集会
  • Place of Presentation: 札幌
  • Year and Date: 2009-09-17
• [Presentation] 人獣共通感染症としてのインフルエンザ (2009)
  • Author(s): 高田礼人
  • Organizer: 第47回全国大学保健管理研究集会
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2009-09-17
• [Book] インフルエンザウイルスの抗原変異予測とワクチン (2009)
  • Author(s): 伊藤公人,高田礼人
• [Book] インフルエンザウイルスの基礎月間化学64 (2009)
  • Author(s): 高田礼人
• [Book] 特集パンデミックインフルエンザ
  • Author(s): 高田礼人
  • Publisher: インフルエンザウイルスに対する免疫応答・感染防御機構
• [Remarks] ホームページでの研究成果公開。
• [Patent(Industrial Property Rights)] インフルエンザウイルスに対する抗体およびその利用 (2009)
  • Inventor(s): 樋口恵,鈴木定彦,高田礼人,喜田宏,吉田玲子,五十嵐学,宮本洋子
  • Industrial Property Rights Holder: 科学技術振興機構,国立大学法人北海道大学
  • Industrial Property Number: 2009-275367
  • Filing Date: 2009-12-03