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

Viruses. 2023 Mar 6;15(3):687. doi: 10.3390/v15030687.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • Turbinates*
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This study was partly supported by funding from the Emergency Collaborative Project (EKPG22-01 to K.-Y.Y. and J.F.-W.C.) of Guangzhou Laboratory; the Emergency COVID-19 Project (2021YFC0866100 to K.-Y.Y. and J.F.-W.C.), the Major Projects on Public Security, National Key Research and Development Program; the Health and Medical Research Fund (COVID1903010–Projects 7 to J.F.-W.C.), the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region; the Collaborative Research Fund (C7060-21G to J.F.-W.C.) and Theme-Based Research Scheme (T11-709/21-N to D,-Y.J.), the Research Grants Council of the Hong Kong Special Administrative Region; Health@InnoHK, the Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region (to K.-Y.Y. and J.F.-W.C.); the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government (to K.-Y.Y. and J.F.-W.C.); the Major Science and Technology Program of Hainan Province (ZDKJ202003) (to F.Y.); the research project of Hainan Academician Innovation Platform (YSPTZX202004) (to F.Y.); the Hainan Talent Development Project (SRC200003) (to F.Y.); the University of Hong Kong Outstanding Young Researcher Award (to J.F.-W.C.); and the University of Hong Kong Research Output Prize (Li Ka Shing Faculty of Medicine) (to J.F.-W.C.); and donations from the Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, May Tam Mak Mei Yin, the Lee Wan Keung Charity Foundation Limited, the Providence Foundation Limited (in memory of the late Lui Hac Minh), the Hong Kong Sanatorium and Hospital, Hui Ming, Hui Hoy and the Chow Sin Lan Charity Fund Limited, the Chen Wai Wai Vivien Foundation Limited, the Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, the Jessie and George Ho Charitable Foundation, the Perfect Shape Medical Limited, Kai Chong Tong, Tse Kam Ming Laurence, the Foo Oi Foundation Limited, Betty Hing-Chu Lee, Ping Cham So, and the Lo Ying Shek Chi Wai Foundation. The funding sources had no role in the study design, data collection, analysis, interpretation, or writing of the report.