A single blind, placebo-controlled randomized study of the safety, reactogenicity and immunogenicity of the “EpiVacCorona” Vaccine for the prevention of COVID-19, in volunteers aged 18–60 years (phase I–II)

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Abstract

Vaccination of the population is one of the most effective countermeasures in responding to the pandemic caused by novel coronavirus infection. Therefore, scientists all over the world have been working to develop effective and safe vaccines. We have developed a synthetic peptide vaccine, EpiVacCorona, against novel SARS-CoV-2 coronavirus, which is a suspension for intramuscular administration containing a composition of chemically synthesized peptide immunogens of the S protein of SARS-CoV-2 coronavirus conjugated to a carrier protein and adsorbed on aluminum hydroxide. Phase I–II clinical trials of the vaccine have started that consist of two stages: Stage 1 is an open study of the safety, reactogenicity, and immunological activity of the vaccine with the involvement of 14 volunteers aged 18–30 years; Stage 2 is a single blind, comparative, randomized placebo-controlled study with the involvement of 86 volunteers. The study involved volunteers aged 18–60 years; the vaccine was injected intramuscularly twice, spaced 21 days apart between injections. All local reactions in response to vaccine administration were mild, such as a short-term pain at the injection site. There were no signs of development of local or systemic adverse reactions. The two-dose vaccination scheme induced the production of antibodies, specific to the antigens that make up the vaccine, in 100% of the volunteers. Seroconversion with a neutralizing antibody titer ≥ 1:20 was reported in 100% of the volunteers 21 days following the second immunization dose. No seroconversion was reported in the groups of volunteers vaccinated with a placebo. The peptide-based EpiVacCorona Vaccine has low reactogenicity and is a safe, immunogenic product. Clinical Trials Identifier: NCT04527575.

About the authors

A. B. Ryzhikov

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Author for correspondence.
Email: ryzhik@vector.nsc.ru

Aleksandr B. Ryzhikov - PhD (Biology), Head of the Department of Zoonotic Infections and Influenza.

630559, Novosibirsk Region, Koltsovo.

Phone: +7 (383) 363-47-00 (add. 27-62)

Fax: +7 (383) 336-74-09

Россия

Е. А. Ryzhikov

LLC “EpiVac”

Email: e.a.ryzhikov@gmail.com

Director of LLC “EpiVac”.

Koltsovo, Novosibirsk Region.

Россия

M. P. Bogryantseva

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: bogryantseva@vector.nsc.ru

PhD (Biology), Head of the Biological and Technology Supervision Department.

630559, Novosibirsk Region, Koltsovo.

Россия

S. V. Usova

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: usova_sv@vector.nsc.ru

PhD (Medicine), Leading Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

E. D. Danilenko

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: danilenko_ed@vector.nsc.ru

PhD (Biology), Director of the Medical Biotechnology Institute.

630559, Novosibirsk Region, Koltsovo.

Россия

E. A. Nechaeva

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: nechaeva@vector.nsc.ru

PhD (Medicine), Deputy Director.

630559, Novosibirsk Region, Koltsovo.

Россия

O. V. Pyankov

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: pyankov@vector.nsc.ru

PhD (Biology), Head of the Microorganisms Collection Department.

630559, Novosibirsk Region, Koltsovo.

Россия

O. G. Pyankova

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: pyankova_og@vector.nsc.ru

Leading Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

A. S. Gudymo

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: gudymo_as@vector.nsc.ru

Junior Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

S. A. Bodnev

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: bodnev@vector.nsc.ru

PhD (Medicine), Leading Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

G. S. Onkhonova

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: onhonova_gs@vector.nsc.ru

Junior Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

E. S. Sleptsova

LLC “EpiVac”

Email: katyuss@yandex.ru

Head of the Quality Control Department.

Koltsovo, Novosibirsk Region.

Россия

V. I. Kuzubov

Medical Unit No. 163 of the Federal Medical and Biological Agency of Russia

Email: msch163@fmbamail.ru

Head of the Medical Unit No. 163.

Koltsovo, Novosibirsk Region.

Россия

N. N. Ryndyuk

Medical Unit No. 163 of the Federal Medical and Biological Agency of Russia

Email: help70@mail.ru

Deputy Head of the Medical Unit, Neurologist.

Koltsovo, Novosibirsk Region.

Россия

Z. I. Ginko

Medical Unit No. 163 of the Federal Medical and Biological Agency of Russia

Email: ginko1948@mail.ru

Head of the Especially Dangerous Infections Facility, Plague Control Station, Infectologist.

Koltsovo, Novosibirsk Region.

Россия

V. N. Petrov

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: vnpetrov@vector.nsc.ru

Head of the Information and Analytical Department.

630559, Novosibirsk Region, Koltsovo.

Россия

A. A. Moiseeva

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: chalaya_aa@vector.nsc.ru

Junior Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

P. Yu. Torzhkova

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: torzhkova_pyu@vector.nsc.ru

Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

S. A. Pyankov

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: pyankov_sa@vector.nsc.ru

Leading Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

T. V. Tregubchak

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: treg-@mail.ru

Leading Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

D. V. Antonec

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: antonec@yandex.ru

PhD (Biology), Senior Researcher.

630559, Novosibirsk Region, Koltsovo.

Россия

E. V. Gavrilova

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: gavrilova_ev@vector.nsc.ru

PhD (Biology), Deputy Director for Academic Affairs.

630559, Novosibirsk Region, Koltsovo.

Россия

R. A. Maksyutov

State Scientific Center of Virology and Biotechnology “Vector” of Rospotrebnadzor

Email: maksyutov_ra@vector.nsc.ru

PhD, MD (Biology), Director General.

630559, Novosibirsk Region, Koltsovo.

Россия

References

  1. Ганеева Л.А., Скрипова В.С., Касатова Л.В., Набиуллина Р.М., Абрамова З.И. Оценка некоторых биохимических параметров энергетического обмена у студентов-легкоатлетов после продолжительной нагрузки // Ученые записки Казанского университета. Серия «Естественные науки». 2013. Т. 155, № 1. С. 40–49.
  2. Методы определения показателей качества иммунобиологических препаратов для профилактики и диагностики гриппа: Методические указания МУ 3.3.2.1758-03 // М.: Федеральный центр госсанэпиднадзора Минздрава России, 2005. 44 с.
  3. Berger A., Drosten C., Doerr H.W., Sturmer M., Preiser W. Severe acute respiratory syndrome (SARS) — paradigm of an emerging viral infection. J. Clin. Virol., 2004, vol. 29, pp. 13–22. doi: 10.1016/j.jcv.2003.09.011
  4. Dutta N.K., Mazumdar K., Gordy J.T. The nucleocapsid protein of SARS-CoV-2: a target for vaccine development. J. Virol., 2020, vol. 94, no. 13: e00647-20. doi: 10.1128/JVI.00647-20
  5. Elbe S., Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health. Global Challenges (Hoboken, NJ), 2017, vol. 1, no. 1, pp. 33–46. doi: 10.1002/gch2.1018
  6. Ferretti A.P., Kula T., Wang Y., Nguyen D.M.V., Weinheimer A., Dunlap G.S., Xu Q., Nabilsi N., Perullo C.R., Cristofaro A.W., Whitton H.J., Virbasius A., Olivier K.J. Jr, Buckner L.R., Alistar A.T., Whitman E.D., Bertino S.A., Chattopadhyay S., MacBeath G. Unbiased screens show CD8+ T cells of COVID-19 patients recognize shared epitopes in SARS-CoV-2 that largely reside outside the spike protein. Immunity, 2020, vol. 53, no. 5: 1095–1107.e3. doi: 10.1016/j.immuni.2020.10.006
  7. Goncharova E., Ryzhikov E., Poryvaev V., Bulychev L., Karpyshev N., Maksyutov A., Ryzhikov A. Intranasal immunization with inactivated tick-borne encephalitis virus and the antigenic peptide 89-119 protects mice against intraperitoneal challenge. Int. J. Med. Microbiol., 2006, vol. 296, pp. 195–201. doi: 10.1016/j.ijmm.2006.02.002
  8. He J., Huang J.R., Zhang Y.L., Zhang J. SARS-CoV-2 nucleocapsid protein intranasal inoculation induces local and systemic T cell responses in mice. J. Med. Virol., 2021, vol. 93, pp. 1923–1925. doi: 10.1002/jmv.26769
  9. Kaur S.P., Gupta V. COVID-19 vaccine: a comprehensive status report. Virus Res., 2020, vol. 288: 198114. doi: 10.1016/j.virusres.2020.198114
  10. Khuroo M.S., Khuroo M., Khuroo M.S., Sofi A.A., Khuroo N.S.. COVID-19 Vaccines: a race against time in the middle of death and devastation! J. Clin. Exp. Hepatol., 2020, vol.10, no. 6, pp. 610–621. doi: 10.1371/journal.pntd.0002787
  11. Maksyutov A.Z., Bachinskii A.G., Bazhan S.I., Ryzhikov E.A. Design of safe AIDS vaccines based on search for local similarities between HIV-1 and human proteins. In: AIDS Vaccines and Related Topics. Kerala: Research Signpost, 2004, pp. 47–62.
  12. Patent No. WO 2004/031212. 2004 A1. Russian Federation, Int. Cl. WO 2004/031212. 2004 A1. Antigenic peptides. No. 2003/000421; application: 2003.09.25: date of publication 2004.04.15 / Maksyutov A.Z., Ryzhikov A.B., Kolobov A.A., Maksyutov Z.A. Proprietors: Gosydarstvenyi Nauchnyi Tsentr Virusologii I Biotekhnologii “Vector” Rospotrebnadzora (GNII VB “Vector”). 84 p.
  13. Musicò A., Frigerio R., Mussida A., Barzon L., Sinigaglia A., Riccetti S., Gobbi F., Piubelli C., Bergamaschi G., Chiari M., Gori A., Cretich M. SARS-CoV-2 epitope mapping on microarrays highlights strong immune-response to N protein region. Vaccines, 2021, vol. 9, no. 1: 35. doi: 10.3390/vaccines9010035
  14. Nikolaev E.N., Indeykina M.I., Brzhozovskiy A.G., Bugrova A.E., Kononikhin A.S., Starodubtseva N.L., Petrotchenko E.V., Kovalev G.I., Borchers C.H., Sukhikh G.T. Mass-spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via nucleocapsid N protein. J. Proteome Res., 2020, vol. 19, no. 11, pp. 4393–4397. doi: 10.1021/acs.jproteome.0c00412
  15. Omrani A.S., Saad M.M., Baig K., Bahloul A., Abdul-Matin M., Alaidaroos A.Y., Almakhlafi G.A., Albarrak M.M., Memish Z.A., Albarrak A.M. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect. Dis., 2014, vol. 14, no. 11, pp. 1090–1095. doi: 10.1016/S1473-3099(14)70920-X
  16. R: a language and environment for statistical computing (v.4.0.2). Global Diversity Information Facility. URL: https://www.gbif.org/ru/tool/81287/r-a-language-and-environment-for-statistical-computing
  17. Schiffman F.J. Hematologic pathophysiology. Philadelphia: Lippincott-Raven, 2009. 388 p.
  18. Shrock E., Fujimura E., Kula T., Timms R.T., Lee I.H., Leng Y., Robinson M.L., Sie B.M., Li M.Z., Chen Y., Logue J., Zuiani A., McCulloch D., Lelis F.J.N., Henson S., Monaco D.R., Travers M., Habibi S., Clarke W.A., Caturegli P., Laeyendecker O., Piechocka-Trocha A., Li J.Z., Khatri A., Chu H.Y.; MGH COVID-19 Collection & Processing Team, Villani A.C., Kays K., Goldberg M.B., Hacohen N., Filbin M.R., Yu X.G., Walker B.D., Wesemann D.R., Larman H.B., Lederer J.A., Elledge S.J. Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science, 2020, vol. 370, no. 652: eabd4250. doi: 10.1126/science.abd4250
  19. Song W., Gui M., Wang X., Xiang Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog., 2018, vol. 14, no. 8: e1007236. doi: 10.1371/journal.ppat.1007236
  20. Takeshita M., Nishina N., Moriyama S., Takahashi Y., Uwamino Y., Nagata M., Aoki W., Masaki K., Ishii M., Saya H., Kondo Y., Kaneko Y., Suzuki K., Fukunaga K., Takeuchi T.; Keio Donner project. Incomplete humoral response including neutralizing antibodies in asymptomatic to mild COVID-19 patients in Japan. Virology, 2021, vol. 555, pp. 35–43. doi: 10.1016/j.virol.2020.12.020
  21. Wang H., Wu X., Zhang X., Hou X., Liang T., Wang D., Teng F., Dai J., Duan H., Guo S., Li Y., Yu X. SARS-CoV-2 proteome microarray for mapping COVID-19 antibody interactions at amino acid resolution. ACS Cent. Sci., 2020, vol. 6, no. 12, pp. 2238–2249. doi: 10.1021/acscentsci.0c00742
  22. Wang Q., Zhang L., Kuwahara K., Li L., Liu Z., Li T., Zhu H., Liu J., Xu Y., Xie J., Morioka H., Sakaguchi N., Qin C., Liu G. Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in nonhuman primates. ACS Infect. Dis., 2016, vol. 2, no. 5, pp. 361–376. doi: 10.1021/acsinfecdis.6b00006
  23. WHO declares public health emergency for novel coronavirus. Medscape, 2020. URL: https://www.medscape.com/viewarticle/924596
  24. Wu Y., Wang F., Shen C., Peng W., Li D., Zhao C., Li Z., Li S., Bi Y., Yang Y., Gong Y., Xiao H., Fan Z., Tan S., Wu G., Tan W., Lu X., Fan C., Wang Q., Liu Y., Zhang C., Qi J., Gao G.F., Gao F., Liu L. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science, 2020, vol. 368, no. 6496, pp. 1274–1278. doi: 10.1126/science.abc2241
  25. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R., Niu P., Zhan F., Ma X., Wang D., Xu W., Wu G., Gao G.F., Tan W.; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China 2019. N. Engl. J. Med., 2020, vol. 382, no. 8, pp. 727–733. doi: 10.1056/NEJMoa2001017

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Copyright (c) 2021 Ryzhikov A.B., Ryzhikov Е.А., Bogryantseva M.P., Usova S.V., Danilenko E.D., Nechaeva E.A., Pyankov O.V., Pyankova O.G., Gudymo A.S., Bodnev S.A., Onkhonova G.S., Sleptsova E.S., Kuzubov V.I., Ryndyuk N.N., Ginko Z.I., Petrov V.N., Moiseeva A.A., Torzhkova P.Y., Pyankov S.A., Tregubchak T.V., Antonec D.V., Gavrilova E.V., Maksyutov R.A.

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