Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history

ABSTRACT There are challenges in selecting SARS-CoV-2 vaccine compositions, primarily due to divergent infection or vaccination history and immunological biases toward previous strains. In this study, we evaluated humoral immune responses induced by variant-based monovalent vaccines as booster shots...

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Main Authors: Rui Wang, Yuan Lyu, Meng Chen, Lili Sun, Shaozheng Zhou, Yudi Cui, Juan Ma, Desheng Kong, Jianbo Lu, Xuefeng Li, Liangzhi Xie
Format: Article
Language:English
Published: American Society for Microbiology 2025-08-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.02907-24
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author Rui Wang
Yuan Lyu
Meng Chen
Lili Sun
Shaozheng Zhou
Yudi Cui
Juan Ma
Desheng Kong
Jianbo Lu
Xuefeng Li
Liangzhi Xie
author_facet Rui Wang
Yuan Lyu
Meng Chen
Lili Sun
Shaozheng Zhou
Yudi Cui
Juan Ma
Desheng Kong
Jianbo Lu
Xuefeng Li
Liangzhi Xie
author_sort Rui Wang
collection DOAJ
description ABSTRACT There are challenges in selecting SARS-CoV-2 vaccine compositions, primarily due to divergent infection or vaccination history and immunological biases toward previous strains. In this study, we evaluated humoral immune responses induced by variant-based monovalent vaccines as booster shots in mice previously vaccinated with an ancestral strain-based vaccine with or without Omicron BA.5 exposure. Our data suggest that immunological biases toward earlier variants attenuated the potency of variant-based vaccines as a booster dose against subsequent variants, whereas a second booster dose mitigated this effect. Furthermore, in the context of vaccine-induced immunity, prior exposure to Omicron sublineages (e.g., BA.5) attenuated the effect of immunological biases toward earlier variants on the neutralizing potency against Omicron subvariants. In addition, the interval between vaccine doses should also be considered, as an immunologic plateau might occur after repeated vaccination. Furthermore, the XBB.1 monovalent vaccine and a tetravalent vaccine (SCTV01E-2) composed of pre-Omicron variant (Beta) and Omicron subvariants (BA.1, BQ.1.1, and XBB.1) showed comparable neutralizing potency against several Omicron sublineages (BA.1, BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.16, and EG.5) under divergent vaccination history, implicating that multivalent platforms could be explored as a flexible strategy if future strains diverge significantly from current variants.IMPORTANCEContinuous evolution of SARS-CoV-2 variants has raised the need to optimize immunization regimens and update vaccine compositions to protect against the newly emerging variants in the context of repeated vaccination. The significance of this research is briefly summarized as follows:1) Immunological biases toward earlier variants attenuated the potency of variant-based vaccines as a booster dose against subsequent variants, which can be mitigated by a second booster dose.2) In the context of vaccine-induced immunity, a previous exposure to Omicron sublineages, such as BA.5, attenuated the influence of immunological biases toward earlier variants on the neutralizing potency against Omicron subvariants.3) The interval between vaccine doses should be taken into account since an immunologic plateau might occur after repeated vaccination.4) Multivalent vaccines, with epitope diversity, may theoretically enhance the magnitude and breadth of cross-neutralization responses, thereby providing a buffer for unpredictable future variants.
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issn 2165-0497
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publisher American Society for Microbiology
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series Microbiology Spectrum
spelling doaj-art-571e00a156464660898289be39f93dda2025-08-20T03:38:59ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.02907-24Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination historyRui Wang0Yuan Lyu1Meng Chen2Lili Sun3Shaozheng Zhou4Yudi Cui5Juan Ma6Desheng Kong7Jianbo Lu8Xuefeng Li9Liangzhi Xie10Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, ChinaABSTRACT There are challenges in selecting SARS-CoV-2 vaccine compositions, primarily due to divergent infection or vaccination history and immunological biases toward previous strains. In this study, we evaluated humoral immune responses induced by variant-based monovalent vaccines as booster shots in mice previously vaccinated with an ancestral strain-based vaccine with or without Omicron BA.5 exposure. Our data suggest that immunological biases toward earlier variants attenuated the potency of variant-based vaccines as a booster dose against subsequent variants, whereas a second booster dose mitigated this effect. Furthermore, in the context of vaccine-induced immunity, prior exposure to Omicron sublineages (e.g., BA.5) attenuated the effect of immunological biases toward earlier variants on the neutralizing potency against Omicron subvariants. In addition, the interval between vaccine doses should also be considered, as an immunologic plateau might occur after repeated vaccination. Furthermore, the XBB.1 monovalent vaccine and a tetravalent vaccine (SCTV01E-2) composed of pre-Omicron variant (Beta) and Omicron subvariants (BA.1, BQ.1.1, and XBB.1) showed comparable neutralizing potency against several Omicron sublineages (BA.1, BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.16, and EG.5) under divergent vaccination history, implicating that multivalent platforms could be explored as a flexible strategy if future strains diverge significantly from current variants.IMPORTANCEContinuous evolution of SARS-CoV-2 variants has raised the need to optimize immunization regimens and update vaccine compositions to protect against the newly emerging variants in the context of repeated vaccination. The significance of this research is briefly summarized as follows:1) Immunological biases toward earlier variants attenuated the potency of variant-based vaccines as a booster dose against subsequent variants, which can be mitigated by a second booster dose.2) In the context of vaccine-induced immunity, a previous exposure to Omicron sublineages, such as BA.5, attenuated the influence of immunological biases toward earlier variants on the neutralizing potency against Omicron subvariants.3) The interval between vaccine doses should be taken into account since an immunologic plateau might occur after repeated vaccination.4) Multivalent vaccines, with epitope diversity, may theoretically enhance the magnitude and breadth of cross-neutralization responses, thereby providing a buffer for unpredictable future variants.https://journals.asm.org/doi/10.1128/spectrum.02907-24SARS-CoV-2monovalent vaccinesmultivalent vaccinesvaccine-induced immunity
spellingShingle Rui Wang
Yuan Lyu
Meng Chen
Lili Sun
Shaozheng Zhou
Yudi Cui
Juan Ma
Desheng Kong
Jianbo Lu
Xuefeng Li
Liangzhi Xie
Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history
Microbiology Spectrum
SARS-CoV-2
monovalent vaccines
multivalent vaccines
vaccine-induced immunity
title Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history
title_full Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history
title_fullStr Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history
title_full_unstemmed Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history
title_short Immunogenicity of monovalent and multivalent subunit vaccines against SARS-CoV-2 variants in mice with divergent vaccination history
title_sort immunogenicity of monovalent and multivalent subunit vaccines against sars cov 2 variants in mice with divergent vaccination history
topic SARS-CoV-2
monovalent vaccines
multivalent vaccines
vaccine-induced immunity
url https://journals.asm.org/doi/10.1128/spectrum.02907-24
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