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Article: Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals

TitleIntranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals
Authors
Keywords2′-O-methyltransferase
Live attenuated vaccine
Mucosal immunity
NSP16
Sterilizing immunity
T-cell response
Issue Date2022
Citation
Cellular and Molecular Immunology, 2022, v. 19, n. 5, p. 588-601 How to Cite?
AbstractLive attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA, adenoviral vector and inactivated vaccines fail to induce. Here, we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene, which encodes 2′-O-methyltransferase, is catalytically disrupted by a point mutation. This virus, designated d16, was severely attenuated in hamsters and transgenic mice, causing only asymptomatic and nonpathogenic infection. A single dose of d16 administered intranasally resulted in sterilizing immunity in both the upper and lower respiratory tracts of hamsters, thus preventing viral spread in a contact-based transmission model. It also robustly stimulated humoral and cell-mediated immune responses, thus conferring full protection against lethal challenge with SARS-CoV-2 in a transgenic mouse model. The neutralizing antibodies elicited by d16 effectively cross-reacted with several SARS-CoV-2 variants. Secretory immunoglobulin A was detected in the blood and nasal wash of vaccinated mice. Our work provides proof-of-principle evidence for harnessing NSP16-deficient SARS-CoV-2 for the development of live attenuated vaccines and paves the way for further preclinical studies of d16 as a prototypic vaccine strain, to which new features might be introduced to improve safety, transmissibility, immunogenicity and efficacy.
Persistent Identifierhttp://hdl.handle.net/10722/315390
ISSN
2023 Impact Factor: 21.8
2023 SCImago Journal Rankings: 4.838
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYe, Zi Wei-
dc.contributor.authorOng, Chon Phin-
dc.contributor.authorTang, Kaiming-
dc.contributor.authorFan, Yilan-
dc.contributor.authorLuo, Cuiting-
dc.contributor.authorZhou, Runhong-
dc.contributor.authorLuo, Peng-
dc.contributor.authorCheng, Yun-
dc.contributor.authorGray, Victor Sebastien-
dc.contributor.authorWang, Pui-
dc.contributor.authorChu, Hin-
dc.contributor.authorChan, Jasper Fuk Woo-
dc.contributor.authorTo, Kelvin Kai Wang-
dc.contributor.authorChen, Honglin-
dc.contributor.authorChen, Zhiwei-
dc.contributor.authorYuen, Kwok Yung-
dc.contributor.authorLing, Guang Sheng-
dc.contributor.authorYuan, Shuofeng-
dc.contributor.authorJin, Dong Yan-
dc.date.accessioned2022-08-05T10:18:43Z-
dc.date.available2022-08-05T10:18:43Z-
dc.date.issued2022-
dc.identifier.citationCellular and Molecular Immunology, 2022, v. 19, n. 5, p. 588-601-
dc.identifier.issn1672-7681-
dc.identifier.urihttp://hdl.handle.net/10722/315390-
dc.description.abstractLive attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA, adenoviral vector and inactivated vaccines fail to induce. Here, we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene, which encodes 2′-O-methyltransferase, is catalytically disrupted by a point mutation. This virus, designated d16, was severely attenuated in hamsters and transgenic mice, causing only asymptomatic and nonpathogenic infection. A single dose of d16 administered intranasally resulted in sterilizing immunity in both the upper and lower respiratory tracts of hamsters, thus preventing viral spread in a contact-based transmission model. It also robustly stimulated humoral and cell-mediated immune responses, thus conferring full protection against lethal challenge with SARS-CoV-2 in a transgenic mouse model. The neutralizing antibodies elicited by d16 effectively cross-reacted with several SARS-CoV-2 variants. Secretory immunoglobulin A was detected in the blood and nasal wash of vaccinated mice. Our work provides proof-of-principle evidence for harnessing NSP16-deficient SARS-CoV-2 for the development of live attenuated vaccines and paves the way for further preclinical studies of d16 as a prototypic vaccine strain, to which new features might be introduced to improve safety, transmissibility, immunogenicity and efficacy.-
dc.languageeng-
dc.relation.ispartofCellular and Molecular Immunology-
dc.subject2′-O-methyltransferase-
dc.subjectLive attenuated vaccine-
dc.subjectMucosal immunity-
dc.subjectNSP16-
dc.subjectSterilizing immunity-
dc.subjectT-cell response-
dc.titleIntranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41423-022-00855-4-
dc.identifier.pmid35352010-
dc.identifier.pmcidPMC8961489-
dc.identifier.scopuseid_2-s2.0-85127362793-
dc.identifier.hkuros336952-
dc.identifier.volume19-
dc.identifier.issue5-
dc.identifier.spage588-
dc.identifier.epage601-
dc.identifier.eissn2042-0226-
dc.identifier.isiWOS:000774842800001-

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