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
An 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 naïve, 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 × 107 EID50/ dose and 1 × 107.7 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/106 PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/106 PBMC (day 42) from 2.5 SFU/106 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Vaccines - 11(2023), 4 vom: 24. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Ruiqi [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
Date Revised 30.04.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/vaccines11040723 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Zhang, Ruiqi |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a 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 |
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| 520 | |a An 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 naïve, 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 × 107 EID50/ dose and 1 × 107.7 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/106 PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/106 PBMC (day 42) from 2.5 SFU/106 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a DelNS1-nCoV-RBD LAIV | |
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| 700 | 1 | |a Chan, Kwok-Hung |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Pui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Runhong |e verfasserin |4 aut | |
| 700 | 1 | |a Yau, Henry Kwong-Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Creany Ka-Wai |e verfasserin |4 aut | |
| 700 | 1 | |a Au, Meena Wai-Lam |e verfasserin |4 aut | |
| 700 | 1 | |a Tam, Anthony Raymond |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Chi-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Lou, Matthew Kwok-Chung |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Haode |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Shaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Tam, Rachel Chun-Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Teng |e verfasserin |4 aut | |
| 700 | 1 | |a Tsoi, Hoi-Wah |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Miko K W |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jian-Piao |e verfasserin |4 aut | |
| 700 | 1 | |a To, Kelvin Kai-Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Man-Fung |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Honglin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Ivan Fan-Ngai |e verfasserin |4 aut | |
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