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.
<h4>Background</h4>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-control...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0278878 |
| _version_ | 1827967499620057088 |
|---|---|
| author | Dmitry Lioznov Irina Amosova Savely A Sheetikov Ksenia V Zornikova Yana Serdyuk Grigory A Efimov Mikhail Tsyferov Mikhail Khmelevskii Andrei Afanasiev Nadezhda Khomyakova Dmitry Zubkov Anton Tikhonov Tao Zhu Luis Barreto Vitalina Dzutseva |
| author_facet | Dmitry Lioznov Irina Amosova Savely A Sheetikov Ksenia V Zornikova Yana Serdyuk Grigory A Efimov Mikhail Tsyferov Mikhail Khmelevskii Andrei Afanasiev Nadezhda Khomyakova Dmitry Zubkov Anton Tikhonov Tao Zhu Luis Barreto Vitalina Dzutseva |
| author_sort | Dmitry Lioznov |
| collection | DOAJ |
| description | <h4>Background</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>A single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.<h4>Trial registration</h4>Trial registration: ClinicalTrials.gov: NCT04540419. |
| first_indexed | 2024-04-09T18:07:30Z |
| format | Article |
| id | doaj.art-08e8fcb72ba646b8815b34a3a91ff517 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T18:07:30Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-08e8fcb72ba646b8815b34a3a91ff5172023-04-14T05:31:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01183e027887810.1371/journal.pone.0278878Immunogenicity 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 LioznovIrina AmosovaSavely A SheetikovKsenia V ZornikovaYana SerdyukGrigory A EfimovMikhail TsyferovMikhail KhmelevskiiAndrei AfanasievNadezhda KhomyakovaDmitry ZubkovAnton TikhonovTao ZhuLuis BarretoVitalina Dzutseva<h4>Background</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>A single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.<h4>Trial registration</h4>Trial registration: ClinicalTrials.gov: NCT04540419.https://doi.org/10.1371/journal.pone.0278878 |
| spellingShingle | Dmitry Lioznov Irina Amosova Savely A Sheetikov Ksenia V Zornikova Yana Serdyuk Grigory A Efimov Mikhail Tsyferov Mikhail Khmelevskii Andrei Afanasiev Nadezhda Khomyakova Dmitry Zubkov Anton Tikhonov Tao Zhu Luis Barreto Vitalina Dzutseva 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://doi.org/10.1371/journal.pone.0278878 |
| work_keys_str_mv | AT dmitrylioznov immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT irinaamosova immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT savelyasheetikov immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT kseniavzornikova immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT yanaserdyuk immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT grigoryaefimov immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT mikhailtsyferov immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT mikhailkhmelevskii immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT andreiafanasiev immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT nadezhdakhomyakova immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT dmitryzubkov immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT antontikhonov immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT taozhu immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT luisbarreto immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia AT vitalinadzutseva immunogenicityandsafetyofarecombinantadenovirustype5covid19vaccineinadultsdatafromarandomiseddoubleblindplacebocontrolledsingledosephase3trialinrussia |