ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Veterinary Infectious Diseases
Cross-reactivity between antibodies induced by European swine influenza vaccines and Spanish swine influenza strains
Provisionally accepted
- 1Instituto Nacional de Investigación y Tecnología Agroalimentaria (INIA), Madrid, Spain
- 2National Institutes of Health National Cancer Institute, Bethesda, United States
- 3Centro de Investigacion en Sanidad Animal, Valdeolmos, Spain
- 4Icahn School of Medicine at Mount Sinai, New York, United States
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Background. Vaccination is an essential tool for controlling the severity of influenza in swine and its spillover risk to humans. Due to fast mutation rates, genomic reassortment, and the high antigenic variability of influenza A viruses (IAV), it is necessary to update vaccine strains to better match and neutralize circulating viruses. Methods. In this study we analyzed the immune cross-reactivity of hemagglutination inhibition (HI) antibodies induced by currently approved European swine influenza vaccines against Spanish swine influenza viruses (SIVs) isolated from 2016 to 2021 as well as human IAV strains using a murine model. Sera from immunized mice with monovalent (MVV) or trivalent (TVV) swine influenza vaccines were tested against Spanish representative SIVs carrying HAs from different subtypes and lineages using a HI serological assay. Amino acids in the antigenic motifs of the receptor binding site (RBS) of the IAV HA were compared and contrast among SIV strains to detect changes that may affect the protein antigenicity. Results. Sera from mice immunized with MVV or TVV showed no HI antibodies against a 2019 Eurasian avian-like H1 (EAswH1) SIV. The TVV did not induce cross-reactive HI antibodies against two human seasonal H3 SIV from the 2000s (2000s-like H3) or against the human seasonal H3 vaccine strain (HuVacH3). Geometric mean (GM) HI titers of sera from TVV immunized mice were below the protection threshold (GM<40) against the recent human seasonal-like H1 (HUswH1) SIV, against an EAswH1 SIV, and against the human seasonal H1 vaccine strain (HuVacH1). HI antibodies induced by MVV showed high cross-reactivity with a 2019 EAswH1 SIV isolate. Conclusions. Currently authorized vaccines do not induce HI antibodies against some contemporary SIV circulating in Spain, nor to human seasonal influenza vaccine strains. Updating vaccine strains to better match new SIVs emerging in Spanish swine is warranted.
Keywords: Swine, influenza, Vaccine, Public Health, Zoonoses
Received: 15 Oct 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Encinas, Del Real, Nelson, Nogales and García-Sastre. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Paloma Encinas
Gustavo Del Real
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