Affiliation:
1. State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
2. Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 570100, China
3. Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou 570100, China
4. Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong SAR, China
5. Guangzhou Laboratory, Guangdong Province, Guangzhou 510000, China
6. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
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.
Funder
Emergency Collaborative Project of Guangzhou Laboratory
Emergency COVID-19 Project
Health and Medical Research Fund
Collaborative Research Fund
Research Grants Council of the Hong Kong Special Administrative Region
Health@InnoHK
Major Science and Technology Program of Hainan Province
research project of Hainan Academician Innovation Platform
Hainan Talent Development Project
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
Providence Foundation Limited
Hong Kong Sanatorium and Hospital
Hui Ming, Hui Hoy and the Chow Sin Lan Charity Fund Limited
Chen Wai Wai Vivien Foundation Limited
Chan Yin Chuen Memorial Charitable Foundation
Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund
Jessie and George Ho Charitable Foundation
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
Subject
Virology,Infectious Diseases
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