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Infectious Disease Reports
Volume 17
Issue 3
10.3390/idr17030042
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Brief Report

Humoral and Cell-Mediated Immunity Against SARS-CoV-2 in Healthcare Personnel Who Received Multiple mRNA Vaccines: A 4-Year Observational Study

by
Hideaki Kato
1,2,*,
Kaori Sano
3,
Kei Miyakawa
3,
Takayuki Kurosawa
4,
Kazuo Horikawa
2,5,
Yayoi Kimura
2,5,
Atsushi Goto
2,6 and
Akihide Ryo
7
1
Infection Prevention and Control Department, Yokohama City University Hospital, Yokohama 236-0004, Japan
2
Emerging Infectious Diseases Research Center, Yokohama City University Hospital, Yokohama 236-0004, Japan
3
Influenza Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Musashimurayama 208-0011, Japan
4
Clinical Laboratory Department, Yokohama City University Hospital, Yokohama 236-0004, Japan
5
Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
6
Department of Public Health, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
7
Department of Bioinformatics and Integrative Omics, National Institute of Infectious Diseases, Japan Institute for Health Security, Musashimurayama 208-0011, Japan
*
Author to whom correspondence should be addressed.
Infect. Dis. Rep. 2025, 17(3), 42; https://doi.org/10.3390/idr17030042
Submission received: 25 March 2025 / Revised: 23 April 2025 / Accepted: 24 April 2025 / Published: 29 April 2025
(This article belongs to the Special Issue Viral Infectious Diseases: Epidemiology and Prevention Through Vaccination)
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Abstract

Background/Objectives: The long-term effects of multiple updated vaccinations against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have not been clarified. Humoral or cellular immunity dynamics in healthcare workers for four years were analyzed. Methods: Blood samples were collected at five time points from April 2021 to January 2024. Humoral immunity was analyzed using the 50% neutralizing titer (NT50) against the original Omicron XBB and Omicron BA.2.86 strains and cellular immunity were analyzed using the ELISpot interferon-gamma releasing assay. NT50s and the spot-forming count (SFC) of the ELISpot assay were compared in the SARS-CoV-2 Omicron XBB-, Omicron-infected, and uninfected subjects. Results: 32 healthcare workers (median age, 47 years) who received 3–7 vaccine doses were enrolled. The NT50s against the original strain decreased after the second vaccination but were maintained after the third vaccine dose. NT50s against the Omicron XBB and BA.2.86 strains were detected before the Omicron vaccine was introduced and increased following the updated vaccination. The NT50s against the Omicron XBB and BA.2.86 strains were elevated after natural infection by the Omicron strain, albeit without differences compared with the findings in uninfected subjects. Multivariate regression analysis revealed no confounder that affected the antibody titer against the BA.2.86 strain at the fifth blood sampling. The median number of SFCs ranged from 78 to 208 after the first two doses. Conclusions: Multiple vaccinations induced the production of antibodies with divergent activity against emerging mutant strains and enhanced protective effects against the original strain. This finding supported the importance of updated vaccination.
Keywords: SARS-CoV-2; COVID-19; humoral immunity; updated vaccine; cell-mediated immunity; interferon-gamma releasing assay; 50% neutralizing titer; ELISpot; original antigenic sin; antibody divergence SARS-CoV-2; COVID-19; humoral immunity; updated vaccine; cell-mediated immunity; interferon-gamma releasing assay; 50% neutralizing titer; ELISpot; original antigenic sin; antibody divergence

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MDPI and ACS Style

Kato, H.; Sano, K.; Miyakawa, K.; Kurosawa, T.; Horikawa, K.; Kimura, Y.; Goto, A.; Ryo, A. Humoral and Cell-Mediated Immunity Against SARS-CoV-2 in Healthcare Personnel Who Received Multiple mRNA Vaccines: A 4-Year Observational Study. Infect. Dis. Rep. 2025, 17, 42. https://doi.org/10.3390/idr17030042

AMA Style

Kato H, Sano K, Miyakawa K, Kurosawa T, Horikawa K, Kimura Y, Goto A, Ryo A. Humoral and Cell-Mediated Immunity Against SARS-CoV-2 in Healthcare Personnel Who Received Multiple mRNA Vaccines: A 4-Year Observational Study. Infectious Disease Reports. 2025; 17(3):42. https://doi.org/10.3390/idr17030042

Chicago/Turabian Style

Kato, Hideaki, Kaori Sano, Kei Miyakawa, Takayuki Kurosawa, Kazuo Horikawa, Yayoi Kimura, Atsushi Goto, and Akihide Ryo. 2025. "Humoral and Cell-Mediated Immunity Against SARS-CoV-2 in Healthcare Personnel Who Received Multiple mRNA Vaccines: A 4-Year Observational Study" Infectious Disease Reports 17, no. 3: 42. https://doi.org/10.3390/idr17030042

APA Style

Kato, H., Sano, K., Miyakawa, K., Kurosawa, T., Horikawa, K., Kimura, Y., Goto, A., & Ryo, A. (2025). Humoral and Cell-Mediated Immunity Against SARS-CoV-2 in Healthcare Personnel Who Received Multiple mRNA Vaccines: A 4-Year Observational Study. Infectious Disease Reports, 17(3), 42. https://doi.org/10.3390/idr17030042

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