Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine

Abstract BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is...

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Main Authors: Dandan Peng, Tingmei Zhao, Weiqi Hong, Minyang Fu, Cai He, Li Chen, Wenyan Ren, Hong Lei, Jingyun Yang, Aqu Alu, Yanghong Ni, Jian Liu, Jiong Li, Wei Wang, Guobo Shen, Zhiwei Zhao, Li Yang, Jinliang Yang, Zhenling Wang, Yoshimasa Tanaka, Guangwen Lu, Xiangrong Song, Xiawei Wei
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.238
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author Dandan Peng
Tingmei Zhao
Weiqi Hong
Minyang Fu
Cai He
Li Chen
Wenyan Ren
Hong Lei
Jingyun Yang
Aqu Alu
Yanghong Ni
Jian Liu
Jiong Li
Wei Wang
Guobo Shen
Zhiwei Zhao
Li Yang
Jinliang Yang
Zhenling Wang
Yoshimasa Tanaka
Guangwen Lu
Xiangrong Song
Xiawei Wei
author_facet Dandan Peng
Tingmei Zhao
Weiqi Hong
Minyang Fu
Cai He
Li Chen
Wenyan Ren
Hong Lei
Jingyun Yang
Aqu Alu
Yanghong Ni
Jian Liu
Jiong Li
Wei Wang
Guobo Shen
Zhiwei Zhao
Li Yang
Jinliang Yang
Zhenling Wang
Yoshimasa Tanaka
Guangwen Lu
Xiangrong Song
Xiawei Wei
author_sort Dandan Peng
collection DOAJ
description Abstract BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the “priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.
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spelling doaj-art-c5d5e2397951419799d42876e6ce00222025-01-24T05:36:29ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.238Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccineDandan Peng0Tingmei Zhao1Weiqi Hong2Minyang Fu3Cai He4Li Chen5Wenyan Ren6Hong Lei7Jingyun Yang8Aqu Alu9Yanghong Ni10Jian Liu11Jiong Li12Wei Wang13Guobo Shen14Zhiwei Zhao15Li Yang16Jinliang Yang17Zhenling Wang18Yoshimasa Tanaka19Guangwen Lu20Xiangrong Song21Xiawei Wei22Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaCenter for Medical Innovation Nagasaki University Nagasaki JapanLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu ChinaAbstract BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the “priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.https://doi.org/10.1002/mco2.238heterologous vaccinationmRNA vaccinerecombinant RBD vaccineSARS‐CoV‐2
spellingShingle Dandan Peng
Tingmei Zhao
Weiqi Hong
Minyang Fu
Cai He
Li Chen
Wenyan Ren
Hong Lei
Jingyun Yang
Aqu Alu
Yanghong Ni
Jian Liu
Jiong Li
Wei Wang
Guobo Shen
Zhiwei Zhao
Li Yang
Jinliang Yang
Zhenling Wang
Yoshimasa Tanaka
Guangwen Lu
Xiangrong Song
Xiawei Wei
Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
MedComm
heterologous vaccination
mRNA vaccine
recombinant RBD vaccine
SARS‐CoV‐2
title Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
title_full Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
title_fullStr Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
title_full_unstemmed Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
title_short Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine
title_sort heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against ba 4 5 included sars cov 2 variants than homologous vaccination of mrna vaccine
topic heterologous vaccination
mRNA vaccine
recombinant RBD vaccine
SARS‐CoV‐2
url https://doi.org/10.1002/mco2.238
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