Abstract
A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.
Keywords:
COVID-19; SARS-CoV-2; adenovirus; antibody; immune response; vaccine.
MeSH terms
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Adenoviridae / genetics*
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Administration, Intranasal
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Animals
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Antibodies, Neutralizing / blood
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Antibodies, Viral / blood*
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COVID-19
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COVID-19 Vaccines / administration & dosage
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COVID-19 Vaccines / genetics
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COVID-19 Vaccines / immunology*
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Chlorocebus aethiops
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Female
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Genetic Vectors / genetics
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HEK293 Cells
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Humans
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Immunogenicity, Vaccine
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Injections, Intramuscular
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Mice
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Mice, Inbred BALB C
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Pan troglodytes / virology
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Protein Binding
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SARS-CoV-2 / genetics
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SARS-CoV-2 / immunology
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Spike Glycoprotein, Coronavirus / administration & dosage
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / immunology*
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Vaccination
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Vero Cells
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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COVID-19 Vaccines
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
Grants and funding
This work was supported by the National Program on Key Research Project of China [Grant Number 2020YFA0907100]; Chinese Academy of Sciences (CAS) Project for Young Scientists in Basic Research [Grant Number YSBR-010]; Strategic Priority Research Program of the CAS [Grant Number XDB29010202]; National Natural Science Foundation of China (NSFC) [Grant Numbers 81991494], [Grant Number 32041010]; China Postdoctoral Science Foundation [Grant Number 2020T130031ZX]; Youth Innovation Promotion Association CAS [Grant Numbers 2018113], [Grant Number 2017122]; Hainan Province Postdoctoral Science Fund of China [Grant Number 2019-20741].