# Investigation of Potential Cross-Protection Conferred by the Seasonal Influenza Vaccine Against Swine Influenza A Viruses of Pandemic Potential

**Authors:** Alice Lilley, Chiara Chiapponi, Alice Prosperi, Ana Moreno, Laura Soliani, Nicola Lewis, Ruth Harvey

PMC · DOI: 10.3390/vaccines14030211 · Vaccines · 2026-02-26

## TL;DR

This study examines whether the seasonal flu vaccine offers protection against swine influenza viruses that could cause a pandemic.

## Contribution

The study evaluates cross-protection of seasonal influenza vaccines against specific clades of swine influenza A viruses.

## Key findings

- The seasonal vaccine boosts antibody titers in a clade-dependent manner against swine influenza A viruses.
- The 1C.2.1 clade was well recognized by antibodies, but the 1A.3.3.2 clade showed very low recognition.
- Cross-protection varies by lineage, suggesting the vaccine may help during some swine influenza outbreaks.

## Abstract

Background/Objectives: Influenza A viruses cause seasonal epidemics of respiratory infections in humans, the severity of which can be mitigated by influenza vaccine use. Influenza A viruses circulating in pigs continue to pose a pandemic threat, as evidenced by the influenza virus that caused the 2009 pandemic, which originated in pigs. To understand the relative risk of emergence of influenza A viruses from pigs and to assess the potential role of the seasonal influenza vaccine in mitigating this risk, we evaluate the potential cross-protection afforded by the seasonal influenza vaccine against different clades of recently circulating swine influenza A viruses. Methods: The presence of cross-reactive antibodies in pre- and post-vaccination human serum samples was measured in haemagglutination and microneutralisation assays. Representative H1 swine influenza A viruses from different genetic lineages were tested against sera collected after administration of the seasonal influenza vaccine in healthy adult volunteers over a 6-year time-period. Results: Although a clade-dependent boosting of post-vaccination antibody titres was observed, protective titres often failed to be reached. There was heterogeneity in recognition by sera for the contemporary swine influenza A viruses, with the 1C.2.1 clade virus being well recognised in both assays, whilst very low pre- and post-vaccination antibody titres were observed against the 1A.3.3.2 clade (which emerged in pigs following the reverse zoonotic introduction from humans of the A/H1N1 pdm09 virus) by both assays. Conclusions: Seasonal influenza vaccines produce cross-reactive antibodies against some clades of influenza A viruses circulating in pigs, but not all. Depending on the lineage and clade of the virus, the seasonal influenza vaccine might have utility in the event of a swine variant outbreak in humans, whilst a specific vaccine against the outbreak strain is developed.

## Linked entities

- **Diseases:** influenza (MONDO:0005812)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** ST6GAL1 (ST6 beta-galactoside alpha-2,6-sialyltransferase 1) [NCBI Gene 100302026] {aka SIAT1, ST6GalI, ST6N}
- **Diseases:** SwIAV (MESH:D009976), HI (MESH:C565433), Influenza (MESH:D007251), infection (MESH:D007239), respiratory infections (MESH:D012141), injury to (MESH:D014947), deaths (MESH:D003643), respiratory and cardiovascular complications (MESH:D002318)
- **Chemicals:** PBS (MESH:D007854), penicillin (MESH:D010406), CO2 (MESH:D002245), PS (MESH:D010758), DMEM (-), streptomycin (MESH:D013307), TPCK (MESH:D014108)
- **Species:** H3N2 subtype (serotype) [taxon 119210], Paratimomenus sp. DM09 (species) [taxon 307988], Sus scrofa (pig, species) [taxon 9823], H1N1 subtype (serotype) [taxon 114727], Meleagris gallopavo (common turkey, species) [taxon 9103], Mustela putorius furo (black ferret, subspecies) [taxon 9669], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** MDCK — Canis lupus familiaris (Dog), Spontaneously immortalized cell line (CVCL_0422)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13030337/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC13030337/full.md

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Source: https://tomesphere.com/paper/PMC13030337