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Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice

The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion...

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Autores principales: Cai, Jian-Piao, Luo, Cuiting, Wang, Kun, Cao, Hehe, Chen, Lin-Lei, Zhang, Xiaojuan, Han, Yuting, Yin, Feifei, Zhang, Anna Jinxia, Chu, Hin, Yuan, Shuofeng, Kok, Kin-Hang, To, Kelvin Kai-Wang, Chen, Honglin, Chen, Zhiwei, Jin, Dong-Yan, Yuen, Kwok-Yung, Chan, Jasper Fuk-Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052291/
https://www.ncbi.nlm.nih.gov/pubmed/36992395
http://dx.doi.org/10.3390/v15030687
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author Cai, Jian-Piao
Luo, Cuiting
Wang, Kun
Cao, Hehe
Chen, Lin-Lei
Zhang, Xiaojuan
Han, Yuting
Yin, Feifei
Zhang, Anna Jinxia
Chu, Hin
Yuan, Shuofeng
Kok, Kin-Hang
To, Kelvin Kai-Wang
Chen, Honglin
Chen, Zhiwei
Jin, Dong-Yan
Yuen, Kwok-Yung
Chan, Jasper Fuk-Woo
author_facet Cai, Jian-Piao
Luo, Cuiting
Wang, Kun
Cao, Hehe
Chen, Lin-Lei
Zhang, Xiaojuan
Han, Yuting
Yin, Feifei
Zhang, Anna Jinxia
Chu, Hin
Yuan, Shuofeng
Kok, Kin-Hang
To, Kelvin Kai-Wang
Chen, Honglin
Chen, Zhiwei
Jin, Dong-Yan
Yuen, Kwok-Yung
Chan, Jasper Fuk-Woo
author_sort Cai, Jian-Piao
collection PubMed
description The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion vaccine using wild-type SARS-CoV-2 spike induces a much lower serum neutralizing antibody titre against the Omicron subvariants. Since the inactivated vaccine given intramuscularly is one of the most commonly used coronavirus disease 2019 (COVID-19) vaccines in developing regions, we tested the hypothesis that intranasal boosting after intramuscular priming would provide a broader level of protection. Here, we showed that one or two intranasal boosts with the Fc-linked trimeric spike receptor-binding domain from wild-type SARS-CoV-2 can induce significantly higher serum neutralizing antibodies against wild-type SARS-CoV-2 and the Omicron subvariants, including BA.5.2 and XBB.1, with a lower titre in the bronchoalveolar lavage of vaccinated Balb/c mice than vaccination with four intramuscular doses of inactivated whole virion vaccine. The intranasally vaccinated K18-hACE2-transgenic mice also had a significantly lower nasal turbinate viral load, suggesting a better protection of the upper airway, which is the predilected site of infection by Omicron subvariants. This intramuscular priming and intranasal boosting approach that achieves broader cross-protection against Omicron variants and subvariants may lengthen the interval required for changing the vaccine immunogen from months to years.
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spelling pubmed-100522912023-03-30 Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice Cai, Jian-Piao Luo, Cuiting Wang, Kun Cao, Hehe Chen, Lin-Lei Zhang, Xiaojuan Han, Yuting Yin, Feifei Zhang, Anna Jinxia Chu, Hin Yuan, Shuofeng Kok, Kin-Hang To, Kelvin Kai-Wang Chen, Honglin Chen, Zhiwei Jin, Dong-Yan Yuen, Kwok-Yung Chan, Jasper Fuk-Woo Viruses Article The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion vaccine using wild-type SARS-CoV-2 spike induces a much lower serum neutralizing antibody titre against the Omicron subvariants. Since the inactivated vaccine given intramuscularly is one of the most commonly used coronavirus disease 2019 (COVID-19) vaccines in developing regions, we tested the hypothesis that intranasal boosting after intramuscular priming would provide a broader level of protection. Here, we showed that one or two intranasal boosts with the Fc-linked trimeric spike receptor-binding domain from wild-type SARS-CoV-2 can induce significantly higher serum neutralizing antibodies against wild-type SARS-CoV-2 and the Omicron subvariants, including BA.5.2 and XBB.1, with a lower titre in the bronchoalveolar lavage of vaccinated Balb/c mice than vaccination with four intramuscular doses of inactivated whole virion vaccine. The intranasally vaccinated K18-hACE2-transgenic mice also had a significantly lower nasal turbinate viral load, suggesting a better protection of the upper airway, which is the predilected site of infection by Omicron subvariants. This intramuscular priming and intranasal boosting approach that achieves broader cross-protection against Omicron variants and subvariants may lengthen the interval required for changing the vaccine immunogen from months to years. MDPI 2023-03-06 /pmc/articles/PMC10052291/ /pubmed/36992395 http://dx.doi.org/10.3390/v15030687 Text en © 2023 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
Cai, Jian-Piao
Luo, Cuiting
Wang, Kun
Cao, Hehe
Chen, Lin-Lei
Zhang, Xiaojuan
Han, Yuting
Yin, Feifei
Zhang, Anna Jinxia
Chu, Hin
Yuan, Shuofeng
Kok, Kin-Hang
To, Kelvin Kai-Wang
Chen, Honglin
Chen, Zhiwei
Jin, Dong-Yan
Yuen, Kwok-Yung
Chan, Jasper Fuk-Woo
Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice
title Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice
title_full Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice
title_fullStr Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice
title_full_unstemmed Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice
title_short Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice
title_sort intranasal boosting with spike fc-rbd of wild-type sars-cov-2 induces neutralizing antibodies against omicron subvariants and reduces viral load in the nasal turbinate of mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052291/
https://www.ncbi.nlm.nih.gov/pubmed/36992395
http://dx.doi.org/10.3390/v15030687
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