Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

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dc.contributor.authorHenze, Larissa
dc.contributor.authorBraun, Julian
dc.contributor.authorMeyer-Arndt, Lil
dc.contributor.authorJürchott, Karsten
dc.contributor.authorSchlotz, Maike
dc.contributor.authorMichel, Janine
dc.contributor.authorGrossegesse, Marica
dc.contributor.authorMangold, Maike
dc.contributor.authorDingeldey, Manuela
dc.contributor.authorKruse, Beate
dc.contributor.authorHolenya, Pavlo
dc.contributor.authorMages, Norbert
dc.contributor.authorReimer, Ulf
dc.contributor.authorEckey, Maren
dc.contributor.authorSchnatbaum, Karsten
dc.contributor.authorWenschuh, Holger
dc.contributor.authorTimmermann, Bernd
dc.contributor.authorKlein, Florian
dc.contributor.authorNitsche, Andreas
dc.contributor.authorGiesecke-Thiel, Claudia
dc.contributor.authorLoyal, Lucie
dc.contributor.authorThiel, Andreas
dc.date.accessioned2023-03-17T11:46:18Z
dc.date.available2023-03-17T11:46:18Z
dc.date.issued2023-01-31
dc.date.updated2023-02-14T17:40:36Z
dc.description.abstractCurrently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.
dc.identifier.eissn1664-3224
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/18325
dc.identifier.urihttps://doi.org/10.14279/depositonce-17133
dc.language.isoen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.subject.otherSARS-CoV-2
dc.subject.otherantigen-specific T-cells
dc.subject.othercross-reactivity
dc.subject.otherheterologous vaccination
dc.subject.otherhumoral response
dc.titlePrimary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity
dc.typeArticle
dc.type.versionpublishedVersion
dcterms.bibliographicCitation.articlenumber1056525
dcterms.bibliographicCitation.doi10.3389/fimmu.2023.1056525
dcterms.bibliographicCitation.journaltitleFrontiers in Immunology
dcterms.bibliographicCitation.originalpublishernameFrontiers
dcterms.bibliographicCitation.originalpublisherplaceLausanne
dcterms.bibliographicCitation.volume14
dcterms.rightsHolder.referenceCreative-Commons-Lizenz
tub.accessrights.dnbfree
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Medizinische Biotechnologie
tub.publisher.universityorinstitutionTechnische Universität Berlin

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