Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: an open phase I/II trial in healthy adults in Russia

Dolzhikova, I. V.; Zubkova, O. V.; Tukhvatulin, A. I.; Dzharullaeva, A. S.; Tukhvatulina, N. M.; Shcheblyakov, D. V.; Shmarov, M. M.; Tokarskaya, E. A.; Simakova, Y. V.; Egorova, D. A.; Scherbinin, D. N.; Tutykhina, I. L.; Lysenko, A. A.; Kostarnoy, A. V.; Gancheva, P. G.; Ozharovskaya, T. A.; Belugin, B. V.; Kolobukhina, L. V.; Pantyukhov, V. B.; Syromyatnikova, S. I.; Shatokhina, I. V.; Sizikova, T. V.; Rumyantseva, I. G.; Andrus, A. F.; Boyarskaya, N. V.; Voytyuk, A. N.; Babira, V. F.; Volchikhina, S. V.; Kutaev, D. A.; Bel'skih, A. N.; Zhdanov, K. V.; Zakharenko, S. M.; Borisevich, S. V.; Logunov, D. Y.; Naroditsky, B. S.; Gintsburg, A. L.

doi:10.1080/21645515.2016.1238535

Cited by 132Viral Infections and Outbreaks ResearchViral Infections and VectorsPoxvirus research and outbreaks

Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: an open phase I/II trial in healthy adults in Russia

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Dolzhikova, I. V., Zubkova, O. V., Tukhvatulin, A. I., Dzharullaeva, A. S., Tukhvatulina, N. M., Shcheblyakov, D. V., Shmarov, M. M., Tokarskaya, E. A. +28 more·2017·Human Vaccines & Immunotherapeutics

DOI 10.1080/21645515.2016.1238535PMC PMC5360131

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Abstract

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

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Using two different vectors in a heterologous prime-boost schedule can reduce immune responses against vector components that might weaken antigen-induced responses.
“Although adenoviral vectors might induce immune responses against vector components and attenuate antigen-induced responses, prime-boost heterologous vaccination with two different vectors allows minimisation of this effect.9, 10, 11”
From Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia (2021) · cites this paper as [9]
Two immunisations produce a durable and long-lasting immune response.
“Furthermore, the use of two immunisations gives a durable and long-lasting immune response.8, 9”
From Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia (2021) · cites this paper as [9]

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Authors: Dolzhikova, I. V., Zubkova, O. V., Tukhvatulin, A. I., Dzharullaeva, A. S., Tukhvatulina, N. M., Shcheblyakov, D. V., Shmarov, M. M., Tokarskaya, E. A., Simakova, Y. V., Egorova, D. A., Scherbinin, D. N., Tutykhina, I. L., Lysenko, A. A., Kostarnoy, A. V., Gancheva, P. G., Ozharovskaya, T. A., Belugin, B. V., Kolobukhina, L. V., Pantyukhov, V. B., Syromyatnikova, S. I., Shatokhina, I. V., Sizikova, T. V., Rumyantseva, I. G., Andrus, A. F., Boyarskaya, N. V., Voytyuk, A. N., Babira, V. F., Volchikhina, S. V., Kutaev, D. A., Bel'skih, A. N., Zhdanov, K. V., Zakharenko, S. M., Borisevich, S. V., Logunov, D. Y., Naroditsky, B. S., & Gintsburg, A. L.
Affiliations: Ministry of Health of the Russian Federation (RU)
Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health, Moscow, Russia
48 Central Research Institute, Ministry of Defense, Sergiev Posad-6, Russia
No. 7 Main Military Clinical Hospital named after academician N. N. Burdenko, Ministry of Defense, Posad-7, Russia
Military Medical Academy named after S. M. Kirov, Ministry of Defense, Saint Petersburg, Russia
S. M. Kirov Military Medical Academy (RU)
Corresponding author: Logunov, D. Y.
ORCID: Dolzhikova, I. V.
Zubkova, O. V.
Dzharullaeva, A. S.
Tukhvatulina, N. M.
Shcheblyakov, D. V.
Simakova, Y. V.
Egorova, D. A.
Lysenko, A. A.
Kostarnoy, A. V.
Gancheva, P. G.
Belugin, B. V.
Shatokhina, I. V.
Andrus, A. F.
Boyarskaya, N. V.
Zhdanov, K. V.
Zakharenko, S. M.
Borisevich, S. V.
Logunov, D. Y.
Naroditsky, B. S.
Venue: Human Vaccines & Immunotherapeutics
Publisher: Informa UK Limited
Published: 2017-02-02
Volume: 13
Issue: 3
Pages: 613-620
ISSN: 2164-5515 (ISSN-L)
2164-554X
DOI: 10.1080/21645515.2016.1238535
PMC: PMC5360131
OpenAlex: W2584009705
Cited by: 132
References: 18
Citations by year: 2026: 4 · 2025: 15 · 2024: 12 · 2023: 11 · 2022: 14 · 2021: 30 · 2020: 10 · 2019: 14 · 2018: 15 · 2017: 7
FWCI: 9.68
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/3.0/ (vor)
Locations: Human Vaccines & Immunotherapeutics (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
Keywords: Ebola virus disease, vesicular stomatitis virus vector, vaccine safety, immunogenicity, neutralizing antibodies, T cell response, dose escalation, healthy adults
MeSH terms: Adenoviridae, Adolescent, Adult, Animals, Antibodies, Viral, Drug Carriers, Female, Humans, Immunoglobulin G, Leukocytes, Mononuclear, Male, Middle Aged, Pain, Russia, Vaccines, Synthetic, Volunteers, CD4-Positive T-Lymphocytes, Vesiculovirus, CD8-Positive T-Lymphocytes, Hemorrhagic Fever, Ebola, Ebola Vaccines, Young Adult, Antibodies, Neutralizing, Healthy Volunteers, Drug-Related Side Effects and Adverse Reactions

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Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: an open phase I/II trial in healthy adults in Russia

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