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Optimization of A(H1N1)pdm09 vaccine seed viruses: The source of PB1 and HA vRNA as a major determinant for antigen yield

2022-07-02Journal article Restricted access
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dc.contributor.authorAlmeida, Filipe
dc.contributor.authorSantos, Luís A.
dc.contributor.authorTrigueiro-Louro, João M.
dc.contributor.authorRebelo-de-Andrade, Helena
dc.date.accessioned2023-03-20T12:13:10Z
dc.date.available2023-03-20T12:13:10Z
dc.date.issued2022-07-02
dc.description.abstractVaccination prevents and reduces the severity of influenza virus infections. Continuous evolution of influenza hemagglutinin (HA) and neuraminidase (NA) supports the virus to evade pre-existing immunity, which demands vaccines to be reformulated every year. Incorporation of polymerase basic protein 1 (PB1) viral RNA (vRNA) of the same origin of HA and NA vRNA has been observed in previous pandemic viruses and occasionally reported for influenza A vaccine prototype strains of prior seasons. At this point, it remains to be explored whether this phenomenon translates into an improved growth phenotype. In this work, we showed that the HA vRNA of A(H1N1)pdm09 is generally incorporated with the PB1 vRNA of the same origin, establishing the beneficial effect of the presence of PB1 and the pattern of the PB1-HA co-incorporation in the A(H1N1)pdm09 model. We further investigated the putative interplay between PB1 and antigenic proteins regarding the vRNA composition of the progeny and observed that vRNA segregation does not appear to be mainly determined by protein-protein interactions; while vRNA-vRNA interactions can be suggested as the main driving force. Our data also indicate an increase in the hemagglutination capacity and neuraminidase activity due to incorporation of PB1, HA and NA from A(H1N1)pdm09, in comparison with the recombinant virus incorporating only HA and NA from A(H1N1)pdm09 - which have the potential to improve current limitations regarding antigenicity and immunogenicity of influenza vaccines. Further knowledge of the complex vRNA-vRNA interaction network between PB1 and HA will additionally contribute to improve current vaccine formulation, and to gradually optimize the production of A(H1N1)pdm09 reverse genetics vaccine seed virus towards a higher cost-effectiveness.pt_PT
dc.description.abstractHighlights: PB1-HA/NA cosegregation has been observed in influenza A evolution and ecology; PB1 of A(H1N1)pdm09 preferentially incorporated the HA vRNA of the same origin; Viral fitness appears to not be the major driver of vRNA segregation; vRNA-vRNA interaction may represent the major driving force for vRNA composition; Our work potentially contributes for influenza vaccine production optimization.pt_PT
dc.description.sponsorshipThis work is funded by National Funds through the FCT - Fundação para a Ciência e a Tecnologia, I.P., by the FCT project PTDC/SAU-INF/30729/2017; and supported by the PhD grant PD/BD/128402/2017 from FCT PhD Programme in Medicines and Pharmaceutical Innovation (i3DU).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationVirus Res. 2022 Jul 2;315:198795. doi: 10.1016/j.virusres.2022.198795. Epub 2022 Apr 30pt_PT
dc.identifier.doi10.1016/j.virusres.2022.198795pt_PT
dc.identifier.issn0168-1702
dc.identifier.urihttp://hdl.handle.net/10400.18/8569
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationReverse Genetics Vaccine Seeds for Influenza: Mechanisms that drive the co-segregation of PB1 with antigenic proteins
dc.relationNS1 como alvo terapêutico emergente: na procura de novos fármacos contra o vírus influenza
dc.relation.publisherversionhttps://linkinghub.elsevier.com/retrieve/pii/S0168-1702(22)00122-8pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectInfluenzapt_PT
dc.subjectInfluenza A Viruspt_PT
dc.subjectVaccine Seedspt_PT
dc.subjectViral Fitnesspt_PT
dc.subjectHApt_PT
dc.subjectPB1pt_PT
dc.subjectvRNA Segregationpt_PT
dc.subjectInfecções Respiratóriaspt_PT
dc.subjectResistência aos Antimicrobianospt_PT
dc.titleOptimization of A(H1N1)pdm09 vaccine seed viruses: The source of PB1 and HA vRNA as a major determinant for antigen yieldpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleReverse Genetics Vaccine Seeds for Influenza: Mechanisms that drive the co-segregation of PB1 with antigenic proteins
oaire.awardTitleNS1 como alvo terapêutico emergente: na procura de novos fármacos contra o vírus influenza
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-INF%2F30729%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F128402%2F2017/PT
oaire.citation.startPage198795pt_PT
oaire.citation.titleVirus Researchpt_PT
oaire.citation.volume315pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationa0e83cc0-de48-4e03-b202-2e61313186f5
relation.isProjectOfPublication7ea88733-a953-4463-97e1-5a85fe025637
relation.isProjectOfPublication.latestForDiscoverya0e83cc0-de48-4e03-b202-2e61313186f5

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