TY - JOUR

T1 - 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

AU - Lioznov, Dmitry

AU - Amosova, Irina

AU - Sheetikov, Savely A

AU - Zornikova, Ksenia V

AU - Serdyuk, Yana

AU - Efimov, Grigory A

AU - Tsyferov, Mikhail

AU - Khmelevskii, Mikhail

AU - Afanasiev, Andrei

AU - Khomyakova, Nadezhda

AU - Zubkov, Dmitry

AU - Tikhonov, Anton

AU - Zhu, Tao

AU - Barreto, Luis

AU - Dzutseva, Vitalina

N1 - Funding: The study was designed, funded, and managed by NPO Petrovax Pharm LLC (Moscow, Russian Federation). NPO Petrovax Pharm LLC in partnership with CanSino Biologics, Inc. (Tianjin, China) are funding and managing the clinical development of the Ad5-nCoV vaccine in the Russian Federation. MT, MK, DZ, AA, NK, AT and VD are employees of NPO Petrovax Pharm LLC. TZ and LB are employees of CanSino Biologics, Inc. IA, SS, KZ and YS have received funding from NPO Petrovax Pharm LLC for consultation services. DL and GE have received personal fees from NPO Petrovax Pharm LLC for consultation services. The funders had no additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Copyright: © 2023 Lioznov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2023/3/1

Y1 - 2023/3/1

N2 - 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:placebo), 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.

AB - 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:placebo), 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.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85149712035&origin=inward&txGid=0d98e205bb69143d16d9b3935ea08a54

UR - https://www.mendeley.com/catalogue/121435a2-b94f-3118-95f4-fbe7dbedf772/

U2 - 10.1371/journal.pone.0278878

DO - 10.1371/journal.pone.0278878

M3 - Article

C2 - 36888640

VL - 18

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - e0278878

ER -