tetano
Editor, Senior Moderator
PLoS One
. 2023 Mar 8;18(3):e0278878.
doi: 10.1371/journal.pone.0278878. eCollection 2023.
Immunogenicity and safety of a recombinant adenovirus type-5 COVID-19 vaccine in adults: Data from a randomised, double-blind, placebo-controlled, single-dose, phase 3 trial in Russia
Dmitry Lioznov[SUP] 1 2 [/SUP], Irina Amosova[SUP] 1 [/SUP], Savely A Sheetikov[SUP] 3 [/SUP], Ksenia V Zornikova[SUP] 3 [/SUP], Yana Serdyuk[SUP] 3 [/SUP], Grigory A Efimov[SUP] 3 [/SUP], Mikhail Tsyferov[SUP] 4 [/SUP], Mikhail Khmelevskii[SUP] 4 [/SUP], Andrei Afanasiev[SUP] 4 [/SUP], Nadezhda Khomyakova[SUP] 4 [/SUP], Dmitry Zubkov[SUP] 4 [/SUP], Anton Tikhonov[SUP] 4 [/SUP], Tao Zhu[SUP] 5 [/SUP], Luis Barreto[SUP] 5 [/SUP], Vitalina Dzutseva[SUP] 4 6 [/SUP]
Affiliations
Abstract
Background: To determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 1010 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV
lacebo), phase 3 trial (Prometheus).
Methods: From 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Results: Seroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9; 82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2; 93.4) against S protein and 59.0% (95% CI: 53.3; 64.6) seroconversion of neutralising antibodies against SARS-CoV-2 at 28 days post-vaccination were observed. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405 [95% CI: 366; 449]) and S protein (677 [95% CI: 608; 753]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.7 [95% CI: 15.3; 18.3]). Using an IFN-γ ELISpot assay after stimulating the cells with recombinant S protein ectodomain we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically significant compared with the placebo (р<0.001). Systemic reactions were reported in 113 of 496 (22.8%) participants (Ad5-nCoV, 26.9%; Placebo, 10.5%), and local reactions were reported in 108 (21.8%) participants (Ad5-nCoV, 28.5%; Placebo, 1.6%). These were generally mild and resolved within 7 days after vaccination. Of the six serious adverse events reported, none of the events were vaccine related. There were no deaths or premature withdrawals.
Conclusion: A single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.
Trial registration: Trial registration: ClinicalTrials.gov: NCT04540419.
. 2023 Mar 8;18(3):e0278878.
doi: 10.1371/journal.pone.0278878. eCollection 2023.
Immunogenicity and safety of a recombinant adenovirus type-5 COVID-19 vaccine in adults: Data from a randomised, double-blind, placebo-controlled, single-dose, phase 3 trial in Russia
Dmitry Lioznov[SUP] 1 2 [/SUP], Irina Amosova[SUP] 1 [/SUP], Savely A Sheetikov[SUP] 3 [/SUP], Ksenia V Zornikova[SUP] 3 [/SUP], Yana Serdyuk[SUP] 3 [/SUP], Grigory A Efimov[SUP] 3 [/SUP], Mikhail Tsyferov[SUP] 4 [/SUP], Mikhail Khmelevskii[SUP] 4 [/SUP], Andrei Afanasiev[SUP] 4 [/SUP], Nadezhda Khomyakova[SUP] 4 [/SUP], Dmitry Zubkov[SUP] 4 [/SUP], Anton Tikhonov[SUP] 4 [/SUP], Tao Zhu[SUP] 5 [/SUP], Luis Barreto[SUP] 5 [/SUP], Vitalina Dzutseva[SUP] 4 6 [/SUP]
Affiliations
- PMID: 36888640
- DOI: 10.1371/journal.pone.0278878
Abstract
Background: To determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 1010 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV
lacebo), phase 3 trial (Prometheus).Methods: From 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Results: Seroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9; 82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2; 93.4) against S protein and 59.0% (95% CI: 53.3; 64.6) seroconversion of neutralising antibodies against SARS-CoV-2 at 28 days post-vaccination were observed. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405 [95% CI: 366; 449]) and S protein (677 [95% CI: 608; 753]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.7 [95% CI: 15.3; 18.3]). Using an IFN-γ ELISpot assay after stimulating the cells with recombinant S protein ectodomain we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically significant compared with the placebo (р<0.001). Systemic reactions were reported in 113 of 496 (22.8%) participants (Ad5-nCoV, 26.9%; Placebo, 10.5%), and local reactions were reported in 108 (21.8%) participants (Ad5-nCoV, 28.5%; Placebo, 1.6%). These were generally mild and resolved within 7 days after vaccination. Of the six serious adverse events reported, none of the events were vaccine related. There were no deaths or premature withdrawals.
Conclusion: A single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.
Trial registration: Trial registration: ClinicalTrials.gov: NCT04540419.