# Evaluation of Humoral and Cell-Mediated Immunity Induced by Quadrivalent Influenza Vaccine in Pre-COVID-19 Japan

**Authors:** Naruhito Otani, Toshiomi Okuno, Kumiko Yamada, Toshie Tsuchida, Kaori Ishikawa, Kaoru Ichiki, Takashi Ueda, Yoshio Takesue, Satoshi Higasa, Kazuhiko Nakajima

PMC · DOI: 10.3390/v17050626 · Viruses · 2025-04-26

## TL;DR

This study evaluated immune responses to an influenza vaccine in Japan before the pandemic, finding strong antibody and cell-mediated responses.

## Contribution

The study provides empirical evidence on the immunogenicity of IIV4 in Japan before the impact of COVID-19 measures.

## Key findings

- The geometric mean titer ratio for A/H3N2 exceeded EMA criteria, indicating strong humoral immunity.
- IFN-γ responses showed significant activation for all strains, with 32–36% of participants showing notable increases.
- Infection control measures during the pandemic may have altered influenza immunity patterns.

## Abstract

This study aimed to evaluate the humoral and cell-mediated immune responses induced by an inactivated influenza vaccine (IIV4) during the 2019/2020 influenza season in Japan. We collected blood samples from 25 healthy adults before vaccination, 2 weeks post-vaccination, and 5 months post-vaccination. Humoral and cell-mediated immunities were assessed based on hemagglutination inhibition antibody titers and interferon-γ (IFN-γ) levels, respectively. The geometric mean titer ratio for A/H3N2 exceeded 2.5, meeting the criteria outlined by the European Medicines Agency guidelines; other strains did not achieve similar thresholds. IFN-γ responses indicated significant activation for all strains, with 32–36% of participants exhibiting ≥ 1.5-fold increases. Due to the implementation of infection control measures against COVID-19, influenza activity was not observed during the 2020/2021 and 2021/2022 seasons, potentially altering influenza immunity. Our findings highlight the importance of both humoral and cell-mediated immunity in evaluating vaccine immunogenicity.

## Linked entities

- **Proteins:** IFNG (interferon gamma)
- **Diseases:** influenza (MONDO:0005812), COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}
- **Diseases:** infection (MESH:D007239), COVID-19 (MESH:D000086382), influenza (MESH:D007251)
- **Species:** Homo sapiens (human, species) [taxon 9606], H3N2 subtype (serotype) [taxon 119210]

## Full text

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## Figures

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## References

21 references — full list in the complete paper: https://tomesphere.com/paper/PMC12115787/full.md

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Source: https://tomesphere.com/paper/PMC12115787