Safety and Immunogenicity of a Recombinant Two-Component SARS-CoV-2 Protein Vaccine : Randomized, Double-Blind, Placebo-Controlled Phase I and Phase II Studies
© 2023. The Author(s)..
INTRODUCTION: ReCOV is a recombinant protein vaccine that aims to induce cross-neutralization against SARS-CoV-2 variants. The phase I and phase II studies were conducted in New Zealand and the Philippines, respectively, for ReCOV primary series.
METHODS: Both studies were randomized, double-blind, placebo-controlled designed among COVID-19 vaccine-naïve healthy adults who received two doses of study vaccination with a 21-day interval. In phase I, 100 younger (15-55 years) and older (56-80 years) subjects were 4:1 randomized to receive ReCOV (20 µg or 40 µg) or placebo. In the phase II study, 347 subjects (≥ 18 years) were 2:1 randomized to receive 40 µg ReCOV or placebo. Subjects that received ReCOV were followed up for 6 months after the second dosing. The safety outcomes included solicited and unsolicited AEs, SAEs, and AESIs. The immunogenicity outcomes were live-virus neutralizing antibody (NAb) against prototype, while pseudovirus NAbs against several SARS-CoV-2 variants were included in phase II as well.
RESULTS: No related SAE, AESI, or AE leading to early discontinuation were reported. The AE incidences were higher in ReCOV groups than placebo group in phase I while they were similar between study groups in phase II. The majority of solicited AEs were mild or moderate with median duration of 1.0-4.0 days. The common (≥ 10%) solicited AEs in phase I were injection site reactions, headache, pyrexia, fatigue, and myalgia, and common reported (≥ 5%) ones in phase II included injection site pain, headache, and pyrexia. Robust neutralizing activities against the prototype were observed in ReCOV groups, peaking at 14 days post the second dosing: in phase I, the GMTs for 20 μg and 40 μg ReCOV groups were 1643.2 IU/mL (95% CI 1188.5, 2271.9) and 1289.2 IU/mL (95% CI 868.3, 1914.1) in younger adults, and 1122.3 IU/mL (95% CI 722.6, 1743.1) and 680.3 IU/mL (95% CI 440.2, 1051.4) in older adults, respectively, while in the ReCOV group of phase II, the GMTs for subjects with seronegative and seropositive status at baseline were 3741.0 IU/mL (95% CI 3113.4, 4495.0) and 6138.3 IU/mL (95% CI 5255.1, 7169.9), respectively. In phase II, substantial levels of pseudovirus NAbs against SARS-CoV-2 variants were demonstrated; the peak GMTs for prototype, Omicron BA.2, and BA.4/5 were 8857, 4441, and 2644, and 15,667.3, 7334.3, and 4478.8 among seronegative and seropositive subjects, respectively. The neutralization persisted till 6 months post the second dosing, with only 2.5- to 5.2-fold declines for Omicron variants.
CONCLUSIONS: Two doses of 20 µg and 40 µg ReCOV are safe and immunogenic against SARS-CoV-2 prototype. The cross-neutralizing activities against Omicron variants support ReCOV advance to late-stage clinical trials.
TRIAL REGISTRATION: Phase I study, clinicaltrials.gov NCT04818801; phase II study, clinicaltrials.gov NCT05084989.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Infectious diseases and therapy - 13(2024), 1 vom: 01. Jan., Seite 57-78 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wynne, Chris [VerfasserIn] |
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| Links: |
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| Themen: |
Clinical trials |
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| Anmerkungen: |
Date Revised 02.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT05084989, NCT04818801 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1007/s40121-023-00896-w |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365938580 |
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| 245 | 1 | 0 | |a Safety and Immunogenicity of a Recombinant Two-Component SARS-CoV-2 Protein Vaccine |b Randomized, Double-Blind, Placebo-Controlled Phase I and Phase II Studies |
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| 500 | |a ClinicalTrials.gov: NCT05084989, NCT04818801 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a INTRODUCTION: ReCOV is a recombinant protein vaccine that aims to induce cross-neutralization against SARS-CoV-2 variants. The phase I and phase II studies were conducted in New Zealand and the Philippines, respectively, for ReCOV primary series | ||
| 520 | |a METHODS: Both studies were randomized, double-blind, placebo-controlled designed among COVID-19 vaccine-naïve healthy adults who received two doses of study vaccination with a 21-day interval. In phase I, 100 younger (15-55 years) and older (56-80 years) subjects were 4:1 randomized to receive ReCOV (20 µg or 40 µg) or placebo. In the phase II study, 347 subjects (≥ 18 years) were 2:1 randomized to receive 40 µg ReCOV or placebo. Subjects that received ReCOV were followed up for 6 months after the second dosing. The safety outcomes included solicited and unsolicited AEs, SAEs, and AESIs. The immunogenicity outcomes were live-virus neutralizing antibody (NAb) against prototype, while pseudovirus NAbs against several SARS-CoV-2 variants were included in phase II as well | ||
| 520 | |a RESULTS: No related SAE, AESI, or AE leading to early discontinuation were reported. The AE incidences were higher in ReCOV groups than placebo group in phase I while they were similar between study groups in phase II. The majority of solicited AEs were mild or moderate with median duration of 1.0-4.0 days. The common (≥ 10%) solicited AEs in phase I were injection site reactions, headache, pyrexia, fatigue, and myalgia, and common reported (≥ 5%) ones in phase II included injection site pain, headache, and pyrexia. Robust neutralizing activities against the prototype were observed in ReCOV groups, peaking at 14 days post the second dosing: in phase I, the GMTs for 20 μg and 40 μg ReCOV groups were 1643.2 IU/mL (95% CI 1188.5, 2271.9) and 1289.2 IU/mL (95% CI 868.3, 1914.1) in younger adults, and 1122.3 IU/mL (95% CI 722.6, 1743.1) and 680.3 IU/mL (95% CI 440.2, 1051.4) in older adults, respectively, while in the ReCOV group of phase II, the GMTs for subjects with seronegative and seropositive status at baseline were 3741.0 IU/mL (95% CI 3113.4, 4495.0) and 6138.3 IU/mL (95% CI 5255.1, 7169.9), respectively. In phase II, substantial levels of pseudovirus NAbs against SARS-CoV-2 variants were demonstrated; the peak GMTs for prototype, Omicron BA.2, and BA.4/5 were 8857, 4441, and 2644, and 15,667.3, 7334.3, and 4478.8 among seronegative and seropositive subjects, respectively. The neutralization persisted till 6 months post the second dosing, with only 2.5- to 5.2-fold declines for Omicron variants | ||
| 520 | |a CONCLUSIONS: Two doses of 20 µg and 40 µg ReCOV are safe and immunogenic against SARS-CoV-2 prototype. The cross-neutralizing activities against Omicron variants support ReCOV advance to late-stage clinical trials | ||
| 520 | |a TRIAL REGISTRATION: Phase I study, clinicaltrials.gov NCT04818801; phase II study, clinicaltrials.gov NCT05084989 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Recombinant two-component SARS-CoV-2 protein vaccine | |
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| 700 | 1 | |a Jaen, Anjuli May |e verfasserin |4 aut | |
| 700 | 1 | |a Mo, Chen |e verfasserin |4 aut | |
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| 700 | 1 | |a Ma, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qingshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Rendu |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jiaping |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Wenrong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jianhui |e verfasserin |4 aut | |
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| 700 | 1 | |a Liu, Yong |e verfasserin |4 aut | |
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