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Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia

BACKGROUND: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-...

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Autores principales: Logunov, Denis Y, Dolzhikova, Inna V, Zubkova, Olga V, Tukhvatulin, Amir I, Shcheblyakov, Dmitry V, Dzharullaeva, Alina S, Grousova, Daria M, Erokhova, Alina S, Kovyrshina, Anna V, Botikov, Andrei G, Izhaeva, Fatima M, Popova, Olga, Ozharovskaya, Tatiana A, Esmagambetov, Ilias B, Favorskaya, Irina A, Zrelkin, Denis I, Voronina, Daria V, Shcherbinin, Dmitry N, Semikhin, Alexander S, Simakova, Yana V, Tokarskaya, Elizaveta A, Lubenets, Nadezhda L, Egorova, Daria A, Shmarov, Maksim M, Nikitenko, Natalia A, Morozova, Lola F, Smolyarchuk, Elena A, Kryukov, Evgeny V, Babira, Vladimir F, Borisevich, Sergei V, Naroditsky, Boris S, Gintsburg, Alexander L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471804/
https://www.ncbi.nlm.nih.gov/pubmed/32896291
http://dx.doi.org/10.1016/S0140-6736(20)31866-3
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author Logunov, Denis Y
Dolzhikova, Inna V
Zubkova, Olga V
Tukhvatulin, Amir I
Shcheblyakov, Dmitry V
Dzharullaeva, Alina S
Grousova, Daria M
Erokhova, Alina S
Kovyrshina, Anna V
Botikov, Andrei G
Izhaeva, Fatima M
Popova, Olga
Ozharovskaya, Tatiana A
Esmagambetov, Ilias B
Favorskaya, Irina A
Zrelkin, Denis I
Voronina, Daria V
Shcherbinin, Dmitry N
Semikhin, Alexander S
Simakova, Yana V
Tokarskaya, Elizaveta A
Lubenets, Nadezhda L
Egorova, Daria A
Shmarov, Maksim M
Nikitenko, Natalia A
Morozova, Lola F
Smolyarchuk, Elena A
Kryukov, Evgeny V
Babira, Vladimir F
Borisevich, Sergei V
Naroditsky, Boris S
Gintsburg, Alexander L
author_facet Logunov, Denis Y
Dolzhikova, Inna V
Zubkova, Olga V
Tukhvatulin, Amir I
Shcheblyakov, Dmitry V
Dzharullaeva, Alina S
Grousova, Daria M
Erokhova, Alina S
Kovyrshina, Anna V
Botikov, Andrei G
Izhaeva, Fatima M
Popova, Olga
Ozharovskaya, Tatiana A
Esmagambetov, Ilias B
Favorskaya, Irina A
Zrelkin, Denis I
Voronina, Daria V
Shcherbinin, Dmitry N
Semikhin, Alexander S
Simakova, Yana V
Tokarskaya, Elizaveta A
Lubenets, Nadezhda L
Egorova, Daria A
Shmarov, Maksim M
Nikitenko, Natalia A
Morozova, Lola F
Smolyarchuk, Elena A
Kryukov, Evgeny V
Babira, Vladimir F
Borisevich, Sergei V
Naroditsky, Boris S
Gintsburg, Alexander L
author_sort Logunov, Denis Y
collection PubMed
description BACKGROUND: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine. METHODS: We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18–60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875. FINDINGS: Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4(+) and 1·3% CD8(+) with the frozen formulation, and a median cell proliferation of 1·3% CD4(+) and 1·1% CD8(+) with the lyophilised formulation. INTERPRETATION: The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19. FUNDING: Ministry of Health of the Russian Federation.
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spelling pubmed-74718042020-09-04 Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia Logunov, Denis Y Dolzhikova, Inna V Zubkova, Olga V Tukhvatulin, Amir I Shcheblyakov, Dmitry V Dzharullaeva, Alina S Grousova, Daria M Erokhova, Alina S Kovyrshina, Anna V Botikov, Andrei G Izhaeva, Fatima M Popova, Olga Ozharovskaya, Tatiana A Esmagambetov, Ilias B Favorskaya, Irina A Zrelkin, Denis I Voronina, Daria V Shcherbinin, Dmitry N Semikhin, Alexander S Simakova, Yana V Tokarskaya, Elizaveta A Lubenets, Nadezhda L Egorova, Daria A Shmarov, Maksim M Nikitenko, Natalia A Morozova, Lola F Smolyarchuk, Elena A Kryukov, Evgeny V Babira, Vladimir F Borisevich, Sergei V Naroditsky, Boris S Gintsburg, Alexander L Lancet Articles BACKGROUND: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine. METHODS: We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18–60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875. FINDINGS: Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4(+) and 1·3% CD8(+) with the frozen formulation, and a median cell proliferation of 1·3% CD4(+) and 1·1% CD8(+) with the lyophilised formulation. INTERPRETATION: The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19. FUNDING: Ministry of Health of the Russian Federation. Elsevier Ltd. 2020 2020-09-04 /pmc/articles/PMC7471804/ /pubmed/32896291 http://dx.doi.org/10.1016/S0140-6736(20)31866-3 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Articles
Logunov, Denis Y
Dolzhikova, Inna V
Zubkova, Olga V
Tukhvatulin, Amir I
Shcheblyakov, Dmitry V
Dzharullaeva, Alina S
Grousova, Daria M
Erokhova, Alina S
Kovyrshina, Anna V
Botikov, Andrei G
Izhaeva, Fatima M
Popova, Olga
Ozharovskaya, Tatiana A
Esmagambetov, Ilias B
Favorskaya, Irina A
Zrelkin, Denis I
Voronina, Daria V
Shcherbinin, Dmitry N
Semikhin, Alexander S
Simakova, Yana V
Tokarskaya, Elizaveta A
Lubenets, Nadezhda L
Egorova, Daria A
Shmarov, Maksim M
Nikitenko, Natalia A
Morozova, Lola F
Smolyarchuk, Elena A
Kryukov, Evgeny V
Babira, Vladimir F
Borisevich, Sergei V
Naroditsky, Boris S
Gintsburg, Alexander L
Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia
title Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia
title_full Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia
title_fullStr Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia
title_full_unstemmed Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia
title_short Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia
title_sort safety and immunogenicity of an rad26 and rad5 vector-based heterologous prime-boost covid-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from russia
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471804/
https://www.ncbi.nlm.nih.gov/pubmed/32896291
http://dx.doi.org/10.1016/S0140-6736(20)31866-3
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