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Evaluation of a novel intramuscular prime/ intranasal boost vaccination strategy against influenza in the pig model

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dc.contributor.authorAvanthay, Robin
dc.contributor.authorGarcía Nicolás, Obdulio
dc.contributor.authorRuggli, Nicolás
dc.contributor.authorGrau-Roma, Llorenç
dc.contributor.authorSummerfield, Artur
dc.contributor.authorZimmer, Gert
dc.contributor.authorPárraga Ros, Ester
dc.contributor.departmentAnatomía y Anatomía Patológica Comparada
dc.date.accessioned2025-12-23T10:46:02Z
dc.date.available2025-12-23T10:46:02Z
dc.date.copyright© 2024 Avanthay et al.
dc.date.issued2024-08-08
dc.description.abstractLive-attenuated influenza vaccines (LAIV) offer advantages over the commonly used inactivated split influenza vaccines. However, finding the optimal balance between sufficient attenuation and immunogenicity has remained a challenge. We recently developed an alternative LAIV based on the 2009 pandemic H1N1 virus with a truncated NS1 protein and lacking PA-X protein expression (NS1(1–126)-ΔPAX). This virus showed a blunted replication and elicited a strong innate immune response. In the present study, we evaluated the efficacy of this vaccine candidate in the porcine animal model as a pertinent in vivo system. Immunization of pigs via the nasal route with the novel NS1(1–126)-ΔPAX LAIV did not cause disease and elicited a strong mucosal immune response that completely blocked replication of the homologous challenge virus in the respiratory tract. However, we observed prolonged shedding of our vaccine candidate from the upper respiratory tract. To improve LAIV safety, we developed a novel prime/boost vaccination strategy combining primary intramuscular immunization with a haemagglutinin-encoding propagation-defective vesicular stomatitis virus (VSV) replicon, followed by a secondary immunization with the NS1(1– 126)-ΔPAX LAIV via the nasal route. This two-step immunization procedure significantly reduced LAIV shedding, increased the production of specific serum IgG, neutralizing antibodies, and Th1 memory cells, and resulted in sterilizing immunity against homologous virus challenge. In conclusion, our novel intramuscular prime/intranasal boost regimen interferes with virus shedding and transmission, a feature that will help combat influenza epidemics and pandemics.
dc.formatapplication/pdf
dc.format.extent23
dc.identifierhttps://doi.org/10.1371/journal.ppat.1012393
dc.identifier.citationPLoS Pathog 20(8): e1012393.
dc.identifier.eissn1553-7366
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/10201/182289
dc.languageeng
dc.publisherPublic Library of Science
dc.relationThis work has received funding from the Swiss National Science Foundation (SNSF), grant no. 189903 (A.S., G.Z.; https://data.snf.ch/grants/grant/189903). The funders had no role in study
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleEvaluation of a novel intramuscular prime/ intranasal boost vaccination strategy against influenza in the pig model
dc.typeinfo:eu-repo/semantics/article
dspace.entity.typePublicationes
relation.isAuthorOfPublication269b9699-1b31-4bb4-82ab-517084bcf737
relation.isAuthorOfPublication.latestForDiscovery269b9699-1b31-4bb4-82ab-517084bcf737
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