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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.
Lancet. 2020 09 26; 396(10255):887-897.Lct

Abstract

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.

Authors+Show Affiliations

Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia. Electronic address: ldenisy@gmail.com.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Autonomous Educational Institution of Higher Education I M Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.Federal State Autonomous Educational Institution of Higher Education I M Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.Federal State Budgetary Institution "The Main Military Clinical Hospital named after N N Burdenko" of the Ministry of Defence of the Russian Federation, Moscow, Russia.Branch No 7 of the Federal State Budgetary Institution "The Main Military Clinical Hospital named after N N Burdenko" of the Ministry of Defence of the Russian Federation, Moscow, Russia.48 Central Research Institute of the Ministry of Defence of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32896291

Citation

Logunov, Denis Y., et al. "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." Lancet (London, England), vol. 396, no. 10255, 2020, pp. 887-897.
Logunov DY, Dolzhikova IV, Zubkova OV, et al. 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. Lancet. 2020;396(10255):887-897.
Logunov, D. Y., Dolzhikova, I. V., Zubkova, O. V., Tukhvatullin, A. I., Shcheblyakov, D. V., Dzharullaeva, A. S., Grousova, D. M., Erokhova, A. S., Kovyrshina, A. V., Botikov, A. G., Izhaeva, F. M., Popova, O., Ozharovskaya, T. A., Esmagambetov, I. B., Favorskaya, I. A., Zrelkin, D. I., Voronina, D. V., Shcherbinin, D. N., Semikhin, A. S., ... Gintsburg, A. L. (2020). 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. Lancet (London, England), 396(10255), 887-897. https://doi.org/10.1016/S0140-6736(20)31866-3
Logunov DY, et al. 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. Lancet. 2020 09 26;396(10255):887-897. PubMed PMID: 32896291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Logunov,Denis Y, AU - Dolzhikova,Inna V, AU - Zubkova,Olga V, AU - Tukhvatullin,Amir I, AU - Shcheblyakov,Dmitry V, AU - Dzharullaeva,Alina S, AU - Grousova,Daria M, AU - Erokhova,Alina S, AU - Kovyrshina,Anna V, AU - Botikov,Andrei G, AU - Izhaeva,Fatima M, AU - Popova,Olga, AU - Ozharovskaya,Tatiana A, AU - Esmagambetov,Ilias B, AU - Favorskaya,Irina A, AU - Zrelkin,Denis I, AU - Voronina,Daria V, AU - Shcherbinin,Dmitry N, AU - Semikhin,Alexander S, AU - Simakova,Yana V, AU - Tokarskaya,Elizaveta A, AU - Lubenets,Nadezhda L, AU - Egorova,Daria A, AU - Shmarov,Maksim M, AU - Nikitenko,Natalia A, AU - Morozova,Lola F, AU - Smolyarchuk,Elena A, AU - Kryukov,Evgeny V, AU - Babira,Vladimir F, AU - Borisevich,Sergei V, AU - Naroditsky,Boris S, AU - Gintsburg,Alexander L, Y1 - 2020/09/04/ PY - 2020/08/17/received PY - 2020/08/26/revised PY - 2020/08/27/accepted PY - 2020/9/9/pubmed PY - 2020/10/6/medline PY - 2020/9/8/entrez SP - 887 EP - 897 JF - Lancet (London, England) JO - Lancet VL - 396 IS - 10255 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/32896291/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(20)31866-3 DB - PRIME DP - Unbound Medicine ER -