tetano
Editor, Senior Moderator
Viruses
. 2023 Mar 6;15(3):687.
doi: 10.3390/v15030687.
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[SUP] 1 [/SUP], Cuiting Luo[SUP] 1 [/SUP], Kun Wang[SUP] 1 [/SUP], Hehe Cao[SUP] 1 [/SUP], Lin-Lei Chen[SUP] 1 [/SUP], Xiaojuan Zhang[SUP] 1 [/SUP], Yuting Han[SUP] 1 [/SUP], Feifei Yin[SUP] 2 3 [/SUP], Anna Jinxia Zhang[SUP] 1 4 [/SUP], Hin Chu[SUP] 1 4 [/SUP], Shuofeng Yuan[SUP] 1 4 [/SUP], Kin-Hang Kok[SUP] 1 4 [/SUP], Kelvin Kai-Wang To[SUP] 1 4 5 [/SUP], Honglin Chen[SUP] 1 4 5 [/SUP], Zhiwei Chen[SUP] 1 4 5 [/SUP], Dong-Yan Jin[SUP] 4 5 6 [/SUP], Kwok-Yung Yuen[SUP] 1 3 4 5 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 3 4 5 [/SUP]
Affiliations
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.
. 2023 Mar 6;15(3):687.
doi: 10.3390/v15030687.
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[SUP] 1 [/SUP], Cuiting Luo[SUP] 1 [/SUP], Kun Wang[SUP] 1 [/SUP], Hehe Cao[SUP] 1 [/SUP], Lin-Lei Chen[SUP] 1 [/SUP], Xiaojuan Zhang[SUP] 1 [/SUP], Yuting Han[SUP] 1 [/SUP], Feifei Yin[SUP] 2 3 [/SUP], Anna Jinxia Zhang[SUP] 1 4 [/SUP], Hin Chu[SUP] 1 4 [/SUP], Shuofeng Yuan[SUP] 1 4 [/SUP], Kin-Hang Kok[SUP] 1 4 [/SUP], Kelvin Kai-Wang To[SUP] 1 4 5 [/SUP], Honglin Chen[SUP] 1 4 5 [/SUP], Zhiwei Chen[SUP] 1 4 5 [/SUP], Dong-Yan Jin[SUP] 4 5 6 [/SUP], Kwok-Yung Yuen[SUP] 1 3 4 5 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 3 4 5 [/SUP]
Affiliations
- PMID: 36992395
- 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.