Elucidating maternal factors affecting rotavirus vaccine immunogenicity

• Project/Area Number: 17K09102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Epidemiology and preventive medicine
• Research Institution: National Institute of Infectious Diseases (2020-2021); The University of Tokyo (2017-2019)
• Principal Investigator: Takanashi Sayaka 国立感染症研究所, 感染症疫学センター, 主任研究官 (20645709)
• Co-Investigator(Kenkyū-buntansha): 春名 めぐみ 東京大学, 大学院医学系研究科(医学部), 教授 (00332601) ; 安戸 裕貴 山口大学, 大学院医学系研究科, 准教授 (70422285)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ロタウイルス / ワクチン / 母体由来因子 / 母乳 / 胃腸炎 / ロタウイルスワクチン / 急性胃腸炎 / 便 / ワクチン免疫原性 / 免疫原性 / 移行抗体

Outline of Final Research Achievements

Colostrum collected within five days after delivery presented higher neutralizing activity against rotavirus whereas that in the mature milk collected at the time of rotavirus vaccine administration was marginal. The results reassure the importance of colostrum in the infection control for rotavirus gastroenteritis and support the current policy that would not hinder giving breast milk before administration of rotavirus vaccine. Neutralizing activity in the breast milk did not correlate either IgA or IgG in the sample, suggesting that other factors than immunoglobulin could be related to the inhibitory function of breast milk for rotavirus infection. Maternal serum IgG against rotavirus in the seroconverted group (infant serum IgA increased more than two-fold) was significantly higher than that in non-seroconverted group, suggesting that IgG transferred through placenta during the pregnancy could affect the immunogenicity of rotavirus vaccine.

Academic Significance and Societal Importance of the Research Achievements

初乳の抗ロタウイルス活性の高さは、ロタウイルス胃腸炎対策としても初乳が重要であることを示唆すると考えられた。現行の経口ロタウイルスワクチン投与月齢時の母乳では、中和の影響は少なく、ロタウイルスワクチン接種時の断乳の必要性が無いことをサポートする結果と考えられた。中和活性と母乳中抗ロタウイルスIgAの相関は無く、免疫グロブリン以外の成分がウイルス活性を低下させる作用がある可能性が示唆された。母体の血清抗ロタウイルスIgG抗体が高いほど、児の抗体獲得率が低い傾向を示したことが報告されており、経胎盤移行したIgGが、児のロタウイルスワクチンに対する免疫応答を阻害する可能性が示唆された。

Research Products

• [Journal Article] 母乳哺育とロタウイルス感染症 (2022)
  • Author(s): 高梨 さやか
  • Journal Title: 日本母乳哺育学会雑誌 Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Role of rotavirus vaccination on G9P[8] rotavirus strain during a seasonal outbreak in Japan. (2021)
  • Author(s): Kawata K, Hoque SA, Nishimura S, Yagyu F, Islam MT, Sharmin LS, Pham NTK, Onda-Shimizu Y, Quang TD, Takanashi S, Okitsu S, Khamrin P, Maneekarn N, Hayakawa S, Ushijima H.
  • Journal Title: Human Vaccine and Immunotherapy Volume: 17 Issue: 10 Pages: 3613-3618
  • DOI: 10.1080/21645515.2021.1925060
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Detection of Rotavirus Antigenemia by Immunochromatographic Kits: a Case Series. (2021)
  • Author(s): Ushijima H, Hikita T, Kobayashi M, Pham NTK, Onda-Shimizu Y, Kawagishi T, Okitsu S, Kanai Y, Kobayashi T, Phan T, Hoque SA, Takanashi S, Komoto S, Kumthip K, Taniguchi K, Maneekarn N, Hayakawa S, Khamrin P.
  • Journal Title: Clinical Laboratory Volume: 67 Issue: 10/2021 Pages: 2275-2282
  • DOI: 10.7754/clin.lab.2021.210125
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distribution of rotavirus genotypes in Japan from 2015 to 2018: Diversity in genotypes before and after introduction of rotavirus vaccines. (2020)
  • Author(s): Hoque SA, Khandoker N, Thongprachum A, Khamrin P, Takanashi S, Okitsu S,
  • Journal Title: Vaccine Volume: 印刷中 Issue: 23 Pages: 3980-3986
  • DOI: 10.1016/j.vaccine.2020.03.061
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ロタウイルス胃腸炎とMicrobiome (2020)
  • Author(s): 高梨 さやか
  • Journal Title: 臨床とウイルス Volume: 48 Pages: 45-51
• [Journal Article] Determining effectiveness of rotavirus vaccine by immunochromatography and reverse transcriptase polymerase chain reaction: A comparison. (2019)
  • Author(s): Hoque SA, Iizuka I, Kobayashi M, Takanashi S, Anwar KS, Islam MT, Hoque SA, Khamrin P, Okitsu S, Hayakawa S, Ushijima H.
  • Journal Title: Vaccine Volume: 39 Issue: 39 Pages: 5886-5890
  • DOI: 10.1016/j.vaccine.2019.07.091
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular detection of enteric viruses in the stool samples of children without diarrhea in Bangladesh. (2019)
  • Author(s): Okitsu S, Khamrin P, Takanashi S, Thongprachum A, Hoque SA, Takeuchi H, Khan MA, Hasan SMT, Iwata T, Shimizu H, Jimba M, Hayakawa S, Maneekarn N, Ushijima H.
  • Journal Title: Infect Genet Evol Volume: 77 Pages: 104055-104055
  • DOI: 10.1016/j.meegid.2019.104055
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Detection of mutations in the VP7 gene of vaccine-derived strains shed by monovalent rotavirus vaccine recipients. (2019)
  • Author(s): Kaneko M, Takanashi S, Inoue M, Sakiyama H, Okitsu S, Mizuguchi M, Ushijima H
  • Journal Title: Access Microbiology Volume: acmi.0.000033 Issue: 8
  • DOI: 10.1099/acmi.0.000033
  • Peer Reviewed / Open Access
• [Journal Article] How the gut microbiome regulates host immune responses to viral vaccines. (2019)
  • Author(s): Vlasova AN, Takanashi S, Miyazaki A, Rajashekara G, Saif LJ
  • Journal Title: Current opinion in virology Volume: 37 Pages: 16-25
  • DOI: 10.1016/j.coviro.2019.05.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diagnosis of Acute Gastroenteritis with Immunochromatography and Effectiveness of Rotavirus Vaccine in a Japanese Clinic. (2019)
  • Author(s): Kawata K, Hikita T, Takanashi S, Hikita H, Ogita K, Okitsu S, Hoque SA, Phan T G, Ushijima H.
  • Journal Title: Access Microbiol. Volume: acmi.0.000085. Issue: 3
  • DOI: 10.1099/acmi.0.000085
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of rotavirus vaccination on an emerging G8P[8] rotavirus strain causing an outbreak in central Japan (2018)
  • Author(s): Hoque SA, Kobayashi M, Takanashi S, Anwar KS, Watanabe T, Khamrin P, Okitsu S, Hayakawa S, Ushijima H
  • Journal Title: Vaccine Volume: 36 Issue: 1 Pages: 43-49
  • DOI: 10.1016/j.vaccine.2017.11.056
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular epidemiology of rotavirus gastroenteritis in Japan during 2014-2015: Characterization of re-emerging G2P[4] after rotavirus vaccine introduction (2018)
  • Author(s): Khandoker Nusrat、Thongprachum Aksara、Takanashi Sayaka、Okitsu Shoko、Nishimura Shuichi、Kikuta Hideaki、Yamamoto Atsuko、Sugita Kumiko、Baba Tsuneyoshi、Kobayashi Masaaki、Hayakawa Satoshi、Mizuguchi Masashi、Ushijima Hiroshi
  • Journal Title: Journal of Medical Virology Volume: 印刷中 Issue: 6 Pages: 1040-1046
  • DOI: 10.1002/jmv.25067
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Detection and molecular characterization of two rare G8P[14] and G3P[3] rotavirus strains collected from children with acute gastroenteritis in Japan (2018)
  • Author(s): Okitsu S, Hikita T, Thongprachum A, Khamrin P, Takanashi S, Hayakawa S, Maneekarn N, Ushijima H
  • Journal Title: Infect Genet Evol Volume: - Pages: 95-108
  • DOI: 10.1016/j.meegid.2018.04.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of vaccine-derived rotavirus strains in children with acute gastroenteritis in Japan, 2012-2015 (2017)
  • Author(s): Kaneko Mei、Takanashi Sayaka、Thongprachum Aksara、Hanaoka Nozomu、Fujimoto Tsuguto、Nagasawa Koo、Kimura Hirokazu、Okitsu Shoko、Mizuguchi Masashi、Ushijima Hiroshi
  • Journal Title: PLOS ONE Volume: 12 Issue: 9 Pages: e0184067-e0184067
  • DOI: 10.1371/journal.pone.0184067
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular Epidemiological Traits of Group A Rotaviruses in Japanese Children During Transitional Period of Rotavirus Vaccine Implementation, 2011 - 2014. (2017)
  • Author(s): Takanashi S, Thongprachum A, Okitsu S, Nishimura S, Kobayashi M, Kikuta H, Yamamoto A, Sugita K, Baba T, Hayakawa S, Mizuguchi M, Ushijima H
  • Journal Title: Clinical Laboratory Volume: 63 Issue: 05+06/2017 Pages: 961-970
  • DOI: 10.7754/clin.lab.2017.161216
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 母乳哺育とロタウイルス感染症 (2021)
  • Author(s): 高梨 さやか
  • Organizer: 第35回日本母乳哺育学会学術集会
  • Invited
• [Presentation] ロタウイルスワクチン導入前後におけるロタウイルス感染症と遺伝子型の動向 (2020)
  • Author(s): 牛島廣治, Hoque SK Ariful, Khamrin Pattara, 高梨さやか, 沖津祥子, 早川智
  • Organizer: 第61回日本臨床ウイルス学会
• [Presentation] Molecular detection of sapovirus in the children with acute gastroenteritis collected from one outpatient clinic in Japan, 2014 to 2017 (2019)
  • Author(s): Okitsu S, Khamrin P, Hikita T, Takanashi S, Hayakawa S, Maneekarn N, Ushijima H
  • Organizer: 7th International Calicivirus Conference
  • Int'l Joint Research
• [Presentation] Detection of gastroenteritis viruses in environmental rain waters and dusts (2019)
  • Author(s): Ushijima H, Kawata K, Okuda T, Hoque A, Nomura A, Shimizu-Onda Y, Okitsu S, Khamrin P, Takanashi S, Hayakawa S, Maneekarn N
  • Organizer: 7th International Calicivirus Conference
  • Int'l Joint Research
• [Presentation] イムノクロマト法によるロタウイルス抗原血症の検討 (2019)
  • Author(s): 牛島 廣治、疋田 敏之、Kim Pham、飯塚 愛恵、恩田 優子、川岸 崇裕、金井 裕太、河本聡志、高梨さやか、沖津 祥子、田島 剛、菊田 英明、小林 正明、山本 あつ子、西村 修一、杉田 久美子、馬場 常嘉、小林 剛、谷口 孝喜、早川 智
  • Organizer: 第51回日本小児感染症学会総会・学術集会
• [Presentation] イムノクロマト法による胃腸炎の 診断とロタウイルスワクチンの効果についての検討 (2019)
  • Author(s): 疋田敏之、疋田博之、疋田房子、高梨 さやか、沖津祥子、Hoque Ariful、牛島廣治
  • Organizer: 第51回日本小児感染症学会総会・学術集会
• [Presentation] イムノクロマト法と酵素抗体法によるロタウイルス抗原血症と抗原尿症の検索 (2019)
  • Author(s): 牛島 廣治、塩田 愛恵、清水 優子、宮下 英将、小林 正明、カムリン パタラ、ホク アリフル、高梨さやか、沖津 祥子、川岸 崇裕、金井 裕太、河本聡、谷口 孝喜、小林 剛、田島 剛、マネカンニワット、早川 智
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] 低栄養児由来便細菌叢移植無菌ブタモデルを用いた蛋白質欠乏餌によるヒトロタウイルスワクチン効果減弱の解析 (2019)
  • Author(s): 高梨 さやか、宮崎 綾子、マイケル フシーム、ペイム フランシン、テャンペンチノ ジュリエット、スリバスタナ ヴィシャール、ラジャセカラ ギリシュ、サイフ リンダ、ブラソバ アナスタシア
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] 単価ロタウイルスワクチン培養精製抗原を用いた妊婦血清中抗ロタウイルス抗体価の検討 ワクチン免疫原性に影響を与える母体由来因子の解明を目指して (2019)
  • Author(s): 高梨 さやか, 沖津 祥子, 柴村 美帆, 牛島 廣治
  • Organizer: 第60回日本臨床ウイルス学会
• [Presentation] Molecular Epidemiology of Gastroenteritis Viruses in Pediatric Patients in Japan (2019)
  • Author(s): Khamrin Pattara, 飯塚 愛恵, 沖津 祥子, 高梨 さやか, 早川 智, 牛島 廣治
  • Organizer: 第60回日本臨床ウイルス学会
• [Presentation] Determination of Effectiveness of Rotavirus Vaccine by Immunochromatography and Reverse Transcriptase Polymerase Chain Reaction (2019)
  • Author(s): Hoque Ariful, 飯塚(塩田) 愛恵, 小林 正明, 高梨 さやか, Khamrin Pattara, 沖津 祥子, 早川 智, 牛島 廣治
  • Organizer: 第60回日本臨床ウイルス学会
• [Presentation] 単価ロタウイルスワクチン培養精製抗原を用いた妊婦血清中抗ロタウイルス抗体価の検討 (2019)
  • Author(s): 高梨 さやか, 中村 佳恵, 水野 葉子, 名西 恵子, 星野 愛, 安戸 裕貴, 岡 明, 沖津 祥子, 牛島 廣治, 水口 雅
  • Organizer: 第122回日本小児科学会学術集会
• [Presentation] 単価ロタウイルスワクチン培養精製抗原を用いた妊婦血清中抗ロタウイルス抗体価の検討 (2019)
  • Author(s): 高梨さやか、中村佳恵、水野葉子、名西恵子、柴田明子、星野愛、安戸裕貴、岡明、沖津祥子、牛島廣治、水口雅
  • Organizer: 第122回日本小児科学会学術集会
• [Book] 感染症迅速診断キットを見直すーその有用性と限界 ロタウイルス (2017)
  • Author(s): 高梨さやか
  • Total Pages: 7
  • Publisher: 金原出版
• [Remarks] 東京大学大学院医学系研究科発達医科学 ホームページ
  • URL: http://www.development.m.u-tokyo.ac.jp/