Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19
The emergence of SARS-CoV-2 variants escaping immunity challenges the efficacy of current vaccines. Here, we investigated humoral recall responses and vaccine-mediated protection in Syrian hamsters immunized with the third-generation Comirnaty<sup>®</sup> Omicron XBB.1.5-adapted COVID-19...
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MDPI AG
2024-12-01
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| author | Joran Degryse Elke Maas Ria Lassaunière Katrien Geerts Yana Kumpanenko Birgit Weynand Piet Maes Johan Neyts Hendrik Jan Thibaut Yeranddy A. Alpizar Kai Dallmeier |
| author_facet | Joran Degryse Elke Maas Ria Lassaunière Katrien Geerts Yana Kumpanenko Birgit Weynand Piet Maes Johan Neyts Hendrik Jan Thibaut Yeranddy A. Alpizar Kai Dallmeier |
| author_sort | Joran Degryse |
| collection | DOAJ |
| description | The emergence of SARS-CoV-2 variants escaping immunity challenges the efficacy of current vaccines. Here, we investigated humoral recall responses and vaccine-mediated protection in Syrian hamsters immunized with the third-generation Comirnaty<sup>®</sup> Omicron XBB.1.5-adapted COVID-19 mRNA vaccine, followed by infection with either antigenically closely (EG.5.1) or distantly related (JN.1) Omicron subvariants. Vaccination with the YF17D vector encoding a modified Gamma spike (YF-S0*) served as a control for SARS-CoV-2 immunity restricted to pre-Omicron variants. Our results show that both Comirnaty<sup>®</sup> XBB.1.5 and YF-S0* induce robust, however, poorly cross-reactive, neutralizing antibody (nAb) responses. In either case, total antibody and nAb levels increased following infection. Intriguingly, the specificity of these boosted nAbs did not match the respective challenge virus, but was skewed towards the primary antigen used for immunization, suggesting a marked impact of antigenic imprinting, confirmed by antigenic cartography. Furthermore, limited cross-reactivity and rapid decline in nAbs induced by Comirnaty<sup>®</sup> XBB.1.5 with EG.5.1 and, more concerning, JN.1, raises doubts about sustained vaccine efficacy against recent circulating Omicron subvariants. In conclusion, we demonstrate that antigenic imprinting plays a dominant role in shaping humoral immunity against emerging SARS-CoV-2 variants. Future vaccine design may have to address two major issues: (i) overcoming original antigenic sin that limits the breadth of a protective response towards emerging variants, and (ii) achieving sustained immunity that lasts for at least one season. |
| format | Article |
| id | doaj-art-cbf21bf021e545879e9e8a934e325501 |
| institution | OA Journals |
| issn | 2076-2607 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Microorganisms |
| spelling | doaj-art-cbf21bf021e545879e9e8a934e3255012025-08-20T02:01:20ZengMDPI AGMicroorganisms2076-26072024-12-011212259110.3390/microorganisms12122591Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19Joran Degryse0Elke Maas1Ria Lassaunière2Katrien Geerts3Yana Kumpanenko4Birgit Weynand5Piet Maes6Johan Neyts7Hendrik Jan Thibaut8Yeranddy A. Alpizar9Kai Dallmeier10KU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), 3000 Leuven, BelgiumDepartment of Virus & Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen, DenmarkKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), 3000 Leuven, BelgiumKU Leuven, Department of Imaging and Pathology, Translational Cell and Tissue Research, Division of Translational Cell and Tissue Research, KU Leuven, 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Laboratory of Clinical and Epidemiological Virology, 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory for Virology & Antiviral Research, 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Translational Platform for Virus, Vaccine and Cancer Research (TPVC), 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), 3000 Leuven, BelgiumKU Leuven, Department of Microbiology, Immunology & Transplantation, Rega Institute, Virology, Antiviral Drug and Vaccine Research Group, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), 3000 Leuven, BelgiumThe emergence of SARS-CoV-2 variants escaping immunity challenges the efficacy of current vaccines. Here, we investigated humoral recall responses and vaccine-mediated protection in Syrian hamsters immunized with the third-generation Comirnaty<sup>®</sup> Omicron XBB.1.5-adapted COVID-19 mRNA vaccine, followed by infection with either antigenically closely (EG.5.1) or distantly related (JN.1) Omicron subvariants. Vaccination with the YF17D vector encoding a modified Gamma spike (YF-S0*) served as a control for SARS-CoV-2 immunity restricted to pre-Omicron variants. Our results show that both Comirnaty<sup>®</sup> XBB.1.5 and YF-S0* induce robust, however, poorly cross-reactive, neutralizing antibody (nAb) responses. In either case, total antibody and nAb levels increased following infection. Intriguingly, the specificity of these boosted nAbs did not match the respective challenge virus, but was skewed towards the primary antigen used for immunization, suggesting a marked impact of antigenic imprinting, confirmed by antigenic cartography. Furthermore, limited cross-reactivity and rapid decline in nAbs induced by Comirnaty<sup>®</sup> XBB.1.5 with EG.5.1 and, more concerning, JN.1, raises doubts about sustained vaccine efficacy against recent circulating Omicron subvariants. In conclusion, we demonstrate that antigenic imprinting plays a dominant role in shaping humoral immunity against emerging SARS-CoV-2 variants. Future vaccine design may have to address two major issues: (i) overcoming original antigenic sin that limits the breadth of a protective response towards emerging variants, and (ii) achieving sustained immunity that lasts for at least one season.https://www.mdpi.com/2076-2607/12/12/2591antigenic imprintingneutralizing antibodiesomicron subvariantsmRNA vaccinesvaccine efficacy |
| spellingShingle | Joran Degryse Elke Maas Ria Lassaunière Katrien Geerts Yana Kumpanenko Birgit Weynand Piet Maes Johan Neyts Hendrik Jan Thibaut Yeranddy A. Alpizar Kai Dallmeier Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19 Microorganisms antigenic imprinting neutralizing antibodies omicron subvariants mRNA vaccines vaccine efficacy |
| title | Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19 |
| title_full | Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19 |
| title_fullStr | Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19 |
| title_full_unstemmed | Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19 |
| title_short | Antigenic Imprinting Dominates Humoral Responses to New Variants of SARS-CoV-2 in a Hamster Model of COVID-19 |
| title_sort | antigenic imprinting dominates humoral responses to new variants of sars cov 2 in a hamster model of covid 19 |
| topic | antigenic imprinting neutralizing antibodies omicron subvariants mRNA vaccines vaccine efficacy |
| url | https://www.mdpi.com/2076-2607/12/12/2591 |
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