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An Open, Non-Randomised, 1/2 Phase Study on the Safety, Tolerability, and Immunogenicity of Single Dose 'Sputnik Light' Vaccine for Prevention of Coronavirus Infection in Healthy Adults

106 Pages Posted: 19 Jul 2021

See all articles by Amir I. Tukhvatulin

Amir I. Tukhvatulin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Inna V. Dolzhikova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Dmitry V. Shcheblyakov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Olga V. Zubkova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Alina S. Dzharullaeva

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Anna V. Kovyrshina

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Nadezhda L. Lubenets

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Daria M. Grousova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Alina S. Erokhova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Andrei G. Botikov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Fatima M. Izhaeva

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Olga Popova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Tatiana A. Ozharovskaia

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Ilias B. Esmagambetov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Irina A. Favorskaya

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Denis I. Zrelkin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Daria V. Voronina

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Dmitry N. Shcherbinin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Alexander S. Semikhin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Yana V. Simakova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Elizaveta A. Tokarskaya

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Maksim M. Shmarov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Natalia A. Nikitenko

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Vladimir A. Gushchin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Elena A. Smolyarchuk

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical 19 University of the Ministry of Health of the Russian Federation (Sechenov University)

Tatiana G. Zubkova

"Eco-Safety" Medical Center

Konstantin A. Zakharov

"Eco-Safety" Medical Center

Vasiliy B. Vasilyuk

"Eco-Safety" Medical Center

Sergei V. Borisevich

«48 Central Research Institute» of the Ministry of Defense of the Russian Federation

Boris S. Naroditsky

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Denis Y. Logunov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

Alexander L. Gintsburg

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya”

More...

Abstract

Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by obvious shortage in supply of licensed vaccines. Development of new vaccines that are easy to manufacture and administer is highly desirable to overcome hurdles in vaccine scaling up and distribution, especially in developing countries. In the effort to satisfy vaccine demands we developed a new single dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein – “Sputnik Light”.

Methods: We conducted an open label, two-stage, prospective, non-randomized phase I-II trial aimed to assess safety, tolerability and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-Cov2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). The trial is registered at ClinicalTrials.gov (NCT04713488).

Findings: Between January 14 and 27, 2021, 150 participants were screened, of whom 110 were enrolled. Most of solicited adverse reactions were mild (66.4% from all vaccinees), few were moderate (5.5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-Cov2 antibodies revealed group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data according to pre-existing immunity to SARS-Cov2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (​GMT) 594.4 at a baseline up to 26899 comparing to 29.09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time in seropositive group seroconversion rate by day 42 was 92.9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81.7% (76/93) and 92.9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15.18 and 579.7 in the seronegative and seropositive groups, respectively. Each test to assess cell-mediated immune reactions was carried out on a separate group of 30 volunteers on day 10 upon vaccination. Antigen-specific T cell proliferation, formation of IFNy-producing cells, as well as IFNy secretion were detected in 96.7% (26/27), 96% (24/25) and 96% (24/25) seronegative and in 100% (3/3) 100% (5/5) and 100% (5/5) seropositive vaccinees, correspondingly.

Interpretation: The single dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induced strong humoral and cellular immune responses both in seronegative and seropositive participants. Further investigation is needed to assess the effectiveness of this vaccine against COVID-19 used for primary and secondary vaccination.

Clinical Trial Registration Details: The trial is registered at ClinicalTrials.gov (NCT04713488).

Funding Information: Russian Direct Investment Fund.

Declaration of Interests: OVZ, TAO, IVD, OP, DVS, DMG, ASD, AIT, DNS, IBE, EAT, AGB, ASE, FMI, NAN, NLL, ASS, SVB, BSN, DYL, ALG report patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests.

Ethics Approval Statement: The trial was approved by the local ethic committee and was conducted with the approval of the Ministry of Health of Russian Federation in compliance with International Conference on Harmonization and National Good Clinical Practice guidelines and Declaration of Helsinki.

Suggested Citation

Tukhvatulin, Amir I. and Dolzhikova, Inna V. and Shcheblyakov, Dmitry V. and Zubkova, Olga V. and Dzharullaeva, Alina S. and Kovyrshina, Anna V. and Lubenets, Nadezhda L. and Grousova, Daria M. and Erokhova, Alina S. and Botikov, Andrei G. and Izhaeva, Fatima M. and Popova, Olga and Ozharovskaia, Tatiana A. and Esmagambetov, Ilias B. and Favorskaya, Irina A. and Zrelkin, Denis I. and Voronina, Daria V. and Shcherbinin, Dmitry N. and Semikhin, Alexander S. and Simakova, Yana V. and Tokarskaya, Elizaveta A. and Shmarov, Maksim M. and Nikitenko, Natalia A. and Gushchin, Vladimir A. and Smolyarchuk, Elena A. and Zubkova, Tatiana G. and Zakharov, Konstantin A. and Vasilyuk, Vasiliy B. and Borisevich, Sergei V. and Naroditsky, Boris S. and Logunov, Denis Y. and Gintsburg, Alexander L., An Open, Non-Randomised, 1/2 Phase Study on the Safety, Tolerability, and Immunogenicity of Single Dose 'Sputnik Light' Vaccine for Prevention of Coronavirus Infection in Healthy Adults. Available at SSRN: https://ssrn.com/abstract=3886430 or http://dx.doi.org/10.2139/ssrn.3886430

Amir I. Tukhvatulin (Contact Author)

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Inna V. Dolzhikova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Dmitry V. Shcheblyakov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Olga V. Zubkova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Alina S. Dzharullaeva

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Anna V. Kovyrshina

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Nadezhda L. Lubenets

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Daria M. Grousova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Alina S. Erokhova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Andrei G. Botikov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Fatima M. Izhaeva

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Olga Popova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Tatiana A. Ozharovskaia

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Ilias B. Esmagambetov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Irina A. Favorskaya

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Denis I. Zrelkin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Daria V. Voronina

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Dmitry N. Shcherbinin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Alexander S. Semikhin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Yana V. Simakova

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Elizaveta A. Tokarskaya

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Maksim M. Shmarov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Natalia A. Nikitenko

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Vladimir A. Gushchin

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Elena A. Smolyarchuk

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical 19 University of the Ministry of Health of the Russian Federation (Sechenov University) ( email )

Trubetskaya ul., 8
Moscow
Russia

Tatiana G. Zubkova

"Eco-Safety" Medical Center ( email )

Konstantin A. Zakharov

"Eco-Safety" Medical Center ( email )

Vasiliy B. Vasilyuk

"Eco-Safety" Medical Center ( email )

Sergei V. Borisevich

«48 Central Research Institute» of the Ministry of Defense of the Russian Federation ( email )

Russia

Boris S. Naroditsky

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Denis Y. Logunov

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

Alexander L. Gintsburg

Ministry of Health of the Russian Federation - Federal State Budget Institution, “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” ( email )

Moscow
Russia

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