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

Jian Piao Cai, Cuiting Luo, Kun Wang, Hehe Cao, Lin Lei Chen, Xiaojuan Zhang, Yuting Han, Feifei Yin, Anna Jinxia Zhang, Hin Chu, Shuofeng Yuan, Kin Hang Kok, Kelvin Kai Wang To, Honglin Chen, Zhiwei Chen, Dong Yan Jin, Kwok Yung Yuen, Jasper Fuk Woo Chan

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number687
JournalViruses
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

ASJC Scopus Subject Areas

  • Infectious Diseases
  • Virology

Keywords

  • BA.5.2
  • COVID-19
  • CoronaVac
  • Fc-RBD
  • Omicron variant
  • SARS-CoV-2
  • XBB.1
  • neutralizing antibody

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