Evaluation of the efficacy of SARS-CoV-2 vaccination in elderly people over 80 years old

• Project/Area Number: 22K21115
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0908:Society medicine, nursing, and related fields
• Research Institution: Kobe University
• Principal Investigator: ISHIMARU HANAKO 神戸大学, 医学研究科, 助手 (20965892)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 新型コロナウイルス / ワクチン / COVID-19 / 中和抗体

Outline of Research at the Start

新型コロナウイルス感染症 (COVID-19) 患者の国内死亡率で最も高い世代は80代以上であり、全体の50%を占めている（2022年4月時点）。すなわち、80歳以上高齢者の重症化率および死亡率を抑制することが日本のCOVID-19対策の要となる。本申請研究では80歳以上高齢者に対する新型コロナウイルス（SARS-CoV-2）ワクチン追加接種の有効性および有効期間解明を目指す。そのために、SARS-CoV-2 mRNAワクチンを追加接種した80歳以上高齢者血液検体を用いて、2つの課題（①抗体中和能評価②細胞性免疫評価）に取り組み、SARS-CoV-2流行変異株に対する感染防御能力を追跡調査する。

Outline of Final Research Achievements

We investigated the effect of multiple doses of mRNA vaccine for the newly emerged variants on these populations, cross-neutralizing antibody titers were examined against SARS-CoV-2 variants, including BQ.1.1 and XBB. Blood samples were taken from residents at four long-term care facilities in Hyogo prefecture, Japan (median age, 91 years), after 3rd (n = 67) and 4th (n = 48) mRNA vaccinations, from April to October 2022. After 3rd vaccination, cross-neutralizing antibody prevalence against conventional (D614G) virus, Delta, BA.2, BA.5, BA.2.75, BQ.1.1, and XBB were 100%, 97%, 81%, 51%, 67%, 4%, and 21%, respectively. After 4th vaccination, the antibody positivity rates increased to 100%, 100%, 98%, 79%, 92%, 31%, and 52%, respectively. The 4th vaccination significantly increased cross-neutralizing antibody titers against all tested variants. The positivity rates for BQ.1.1 and XBB increased after 4th vaccination, although the titer value was lower than those of BA.5 and BA.2.75.

Academic Significance and Societal Importance of the Research Achievements

4回目のワクチン接種により、全変異株に対する交差中和抗体価が有意に上昇した。結論 BQ.1.1およびXBBの陽性率は，BA.5およびBA.2.75よりも低かったが，4回目のワクチン接種後に上昇した．ウイルスの急速な変異とワクチンの有効性を考慮すると，ウイルスの流行を考慮し，流行ごとに適したワクチンを開発できるシステムを構築する必要があることが示唆された。本研究は高齢者に対するワクチンの追加接種有効性を示す研究結果となり、今後のSARS-CoV-2感染症対策に貢献する研究成果を得たと考える。

Research Products

• [Journal Article] Fourth mRNA vaccination increases cross-neutralizing antibody titers against SARS-CoV-2 variants, including BQ.1.1 and XBB, in a very elderly population (2023)
  • Author(s): Sutandhio Silvia、Furukawa Koichi、Kurahashi Yukiya、Marini Maria Istiqomah、Effendi Gema Barlian、Hasegawa Natsumi、Ishimaru Hanako、Nishimura Mitsuhiro、Arii Jun、Mori Yasuko
  • Journal Title: Journal of Infection and Public Health Volume: 16 Issue: 7 Pages: 1064-1072
  • DOI: 10.1016/j.jiph.2023.05.004
  • Peer Reviewed / Open Access
• [Journal Article] The Number of Coronavirus Disease 2019 Vaccine Doses and Severe Clinical Outcomes in Older Patients Infected With a Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant (2022)
  • Author(s): Koichi Furukawa, Yukiya Kurahashi, Hanako Ishimaru, Mitsuhiro Nishimura, Jun Arii, Shigeru Sano, Yoshiki Tohma, Hiroyuki Ohkita, Sachiko Nakamura, Sachiyo Iwata, Yasuko Mori
  • Journal Title: The Journal of Infectious Diseases Volume: 226 Issue: 11 Pages: 041-2042
  • DOI: 10.1093/infdis/jiac395
  • Peer Reviewed / Open Access
• [Presentation] Effect of fourth dose mRNA vaccination on emerging SARS-CoV-2 variants (2023)
  • Author(s): Natsumi Hasegawa, Maria Istiqomah Marini, Rei Takamiya, Hanako Ishimaru, Mitsuhiro Nishimura,Jun Arii,Yasuko Mori
  • Organizer: International Society for Vaccines
  • Int'l Joint Research