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The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls f...

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Autores principales: Hu, Longbo, Xu, Yuhua, Wu, Liping, Feng, Jin, Zhang, Lu, Tang, Yongjie, Zhao, Xiang, Mai, Runming, Chen, Liyun, Mei, Lingling, Tan, Yuanzhen, Du, Yingying, Zhen, Yanping, Su, Wenhan, Peng, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146450/
https://www.ncbi.nlm.nih.gov/pubmed/35632595
http://dx.doi.org/10.3390/v14050854
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author Hu, Longbo
Xu, Yuhua
Wu, Liping
Feng, Jin
Zhang, Lu
Tang, Yongjie
Zhao, Xiang
Mai, Runming
Chen, Liyun
Mei, Lingling
Tan, Yuanzhen
Du, Yingying
Zhen, Yanping
Su, Wenhan
Peng, Tao
author_facet Hu, Longbo
Xu, Yuhua
Wu, Liping
Feng, Jin
Zhang, Lu
Tang, Yongjie
Zhao, Xiang
Mai, Runming
Chen, Liyun
Mei, Lingling
Tan, Yuanzhen
Du, Yingying
Zhen, Yanping
Su, Wenhan
Peng, Tao
author_sort Hu, Longbo
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.
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spelling pubmed-91464502022-05-29 The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice Hu, Longbo Xu, Yuhua Wu, Liping Feng, Jin Zhang, Lu Tang, Yongjie Zhao, Xiang Mai, Runming Chen, Liyun Mei, Lingling Tan, Yuanzhen Du, Yingying Zhen, Yanping Su, Wenhan Peng, Tao Viruses Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses. MDPI 2022-04-21 /pmc/articles/PMC9146450/ /pubmed/35632595 http://dx.doi.org/10.3390/v14050854 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hu, Longbo
Xu, Yuhua
Wu, Liping
Feng, Jin
Zhang, Lu
Tang, Yongjie
Zhao, Xiang
Mai, Runming
Chen, Liyun
Mei, Lingling
Tan, Yuanzhen
Du, Yingying
Zhen, Yanping
Su, Wenhan
Peng, Tao
The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
title The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
title_full The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
title_fullStr The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
title_full_unstemmed The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
title_short The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
title_sort e484k substitution in a sars-cov-2 spike protein subunit vaccine resulted in limited cross-reactive neutralizing antibody responses in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146450/
https://www.ncbi.nlm.nih.gov/pubmed/35632595
http://dx.doi.org/10.3390/v14050854
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