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Article: A Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults

TitleA Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults
Authors
KeywordsCOVID-19
DelNS1-nCoV-RBD LAIV
intranasal
phase-1
Issue Date1-Apr-2023
PublisherMDPI
Citation
Vaccines, 2023, v. 11, n. 4 How to Cite?
AbstractAn intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18-55 and COVID-19 vaccines naive, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 x 10(7) EID50/ dose and 1 x 10(7.7) EID50/ dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events (p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/10(6) PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/10(6) PBMC (day 42) from 2.5 SFU/10(6) PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted.
Persistent Identifierhttp://hdl.handle.net/10722/331038
ISSN
2023 Impact Factor: 5.2
2023 SCImago Journal Rankings: 1.201
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, RQ-
dc.contributor.authorChan, KH-
dc.contributor.authorWang, P-
dc.contributor.authorZhou, RH-
dc.contributor.authorYau, HKC-
dc.contributor.authorWong, CKW-
dc.contributor.authorAu, MWL-
dc.contributor.authorTam, AR-
dc.contributor.authorNg, CT-
dc.contributor.authorLou, MKC-
dc.contributor.authorLiu, N-
dc.contributor.authorHuang, HD-
dc.contributor.authorDeng, SF-
dc.contributor.authorTam, RCY-
dc.contributor.authorLiu, Y-
dc.contributor.authorLong, T-
dc.contributor.authorTsoi, HW-
dc.contributor.authorNg, MKW-
dc.contributor.authorCai, JP-
dc.contributor.authorTo, KKW-
dc.contributor.authorYuen, MF-
dc.contributor.authorChen, ZW-
dc.contributor.authorChen, HL-
dc.contributor.authorYuen, KY-
dc.contributor.authorHung, IFN-
dc.date.accessioned2023-09-21T06:52:15Z-
dc.date.available2023-09-21T06:52:15Z-
dc.date.issued2023-04-01-
dc.identifier.citationVaccines, 2023, v. 11, n. 4-
dc.identifier.issn2076-393X-
dc.identifier.urihttp://hdl.handle.net/10722/331038-
dc.description.abstractAn intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18-55 and COVID-19 vaccines naive, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 x 10(7) EID50/ dose and 1 x 10(7.7) EID50/ dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events (p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/10(6) PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/10(6) PBMC (day 42) from 2.5 SFU/10(6) PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted.-
dc.languageeng-
dc.publisherMDPI-
dc.relation.ispartofVaccines-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCOVID-19-
dc.subjectDelNS1-nCoV-RBD LAIV-
dc.subjectintranasal-
dc.subjectphase-1-
dc.titleA Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults-
dc.typeArticle-
dc.identifier.doi10.3390/vaccines11040723-
dc.identifier.pmid37112634-
dc.identifier.scopuseid_2-s2.0-85153719232-
dc.identifier.volume11-
dc.identifier.issue4-
dc.identifier.eissn2076-393X-
dc.identifier.isiWOS:000977808700001-
dc.publisher.placeBASEL-
dc.identifier.issnl2076-393X-

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