Evaluation of specific immune response by varicella vaccine after allogeneic hematopoietic stem cell transplantation

• Project/Area Number: 19K17933
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Tottori University (2020-2021); Jichi Medical University (2019)
• Principal Investigator: KAWAMURA Koji 鳥取大学, 医学部, 講師 (20548763)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 同種造血幹細胞移植 / 水痘・帯状疱疹ウイルス / 弱毒生水痘ワクチン / 麻疹ウイルス / 風疹ウイルス / ムンプスウイルス / 液性免疫 / 細胞性免疫 / 水痘・帯状疱疹 ウイルス / 水痘ワクチン / ウイルス特異的免疫反応

Outline of Research at the Start

本研究は同種造血幹細胞移植後の帯状疱疹に代表される水痘・帯状疱疹ウイルスの再活性化を弱毒生水痘ワクチンの接種によって予防できるかどうかの検証を目的とする。具体的には、同種造血幹細胞移植後に水痘ワクチンを接種した患者の検体を用いて、ウイルス特異的な液性免疫または細胞性免疫の反応が起こっているかを患者ごとに解析し、その結果を実際の臨床経過(再活性化の有無)と統合することで、水痘ワクチンの有効性を評価する。

Outline of Final Research Achievements

I evaluated varicella-zoster virus (VZV)-specific immunity in patients who received live attenuated varicella vaccine after allogeneic hematopoietic stem cell transplantation. CD4+ T-cell count and CD4+ T-cell /CD8+ T-cell ratio at the time of vaccination, and VZV IgG value after vaccination were useful in predicting VZV reactivation after vaccination.
Loss of immunity to measles, mumps, and rubella (MMR) commonly occurs in the first several years posttransplant. In the patients who lose the immunity, seroconversion rate after one dose of MMR vaccine is suboptimal.

Academic Significance and Societal Importance of the Research Achievements

同種造血幹細胞移植後のワクチン接種によって、ウイルス特異的免疫誘導がある程度は得られることが示された。しかし、症例によって反応は様々で、ワクチンの効果がほとんど得られない症例もあり、ワクチン接種前の免疫能の回復の程度がワクチンの効果と相関することが示唆された。同種移植後のVZVをはじめとするウイルスワクチンによる免疫再構築について新たな知見が得られたと同時に、実臨床において同種移植患者のウイルス感染予防法の確立の一助になった。

Research Products

• [Journal Article] Immunity and Vaccination Against Measles, Mumps, and Rubella in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients (2021)
  • Author(s): Koji Kawamura, Hidenori Wada, Hideki Nakasone, Yu Akahoshi, Shunto Kawamura, Junko Takeshita, Nozomu Yoshino, Yukiko Misaki, Kazuki Yoshimura, Ayumi Gomyo, Masaharu Tamaki, Machiko Kusuda, Kazuaki Kameda, Miki Sato, Aki Tanihara, Shun-Ichi Kimura, Shinichi Kako, Yoshinobu Kanda
  • Journal Title: Transplantation and Cellular Therapy Volume: - Issue: 5 Pages: 436.e1-436.e8
  • DOI: 10.1016/j.jtct.2021.02.027
  • Peer Reviewed
• [Presentation] Safety and efficacy of live attenuated varicella vaccine for preventing varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation: A prospective single-center study (2019)
  • Author(s): Kawamura K, Nakasone H, Akahoshi Y, Kawamura S, Takeshita J, Yoshino N, Misaki Y, Yoshimura K, Gomyo A, Tamaki M, Kusuda M, Kameda K, Wada H, Sato M, Terasako-Saito K, Tanihara A, Kimura SI, Kako S, Kanda Y
  • Organizer: The 24th EHA Congress
  • Int'l Joint Research
• [Presentation] Evaluation of the immunity to measles, mumps and rubella in adult patients after allogeneic hematopoietic stem cell transplantation (2019)
  • Author(s): Kawamura K, Nakasone H, Wada H, Akahoshi Y, Kawamura S, Takeshita J, Yoshino N, Misaki Y, Yoshimura K, Gomyo A, Tamaki M, Kusuda M, Kameda K, Sato M, Terasako-Saito K, Tanihara A, Kimura SI, Kako S, Kanda Y
  • Organizer: The 24th EHA Congress
  • Int'l Joint Research
• [Presentation] A prospective single-center study of live attenuated varicella vaccine after allogeneic transplant (2019)
  • Author(s): Kawamura K, Nakasone H, Akahoshi Y, Kawamura S, Takeshita J, Yoshino N, Misaki Y, Yoshimura K, Gomyo A, Tamaki M, Kusuda M, Kameda K, Wada H, Sato M, Terasako-Saito K, Tanihara A, Kimura SI, Kako S, Kanda Y
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] Evaluation of the immunity to measles, mumps and rubella in adult allogeneic transplant patients (2019)
  • Author(s): Kawamura K, Nakasone H, Wada H, Akahoshi Y, Kawamura S, Takeshita J, Yoshino N, Misaki Y, Yoshimura K, Gomyo A, Tamaki M, Kusuda M, Kameda K, Sato M, Terasako-Saito K, Tanihara A, Kimura SI, Kako S, Kanda Y
  • Organizer: 第81回日本血液学会学術集会