Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors

INTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophyla...

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Main Authors: T. A. Ozharovskaia, O. V. Zubkova, O. Popova, A. V. Kovyrshina, P. P. Goldovskaya, I. V. Vavilova, I. V. Dolzhikova, E. I. Ermolova, M. S. Kunda, N. N. Ryzhova, O. L. Voronina, D. N. Shcherbinin, D. V. Shcheblyakov, D. Y. Logunov, A. L. Gintsburg
Format: Article
Language:Russian
Published: Ministry of Health of the Russian Federation. Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» 2024-10-01
Series:Биопрепараты: Профилактика, диагностика, лечение
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Online Access:https://www.biopreparations.ru/jour/article/view/576
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author T. A. Ozharovskaia
O. V. Zubkova
O. Popova
A. V. Kovyrshina
P. P. Goldovskaya
I. V. Vavilova
I. V. Dolzhikova
E. I. Ermolova
M. S. Kunda
N. N. Ryzhova
O. L. Voronina
D. N. Shcherbinin
D. V. Shcheblyakov
D. Y. Logunov
A. L. Gintsburg
author_facet T. A. Ozharovskaia
O. V. Zubkova
O. Popova
A. V. Kovyrshina
P. P. Goldovskaya
I. V. Vavilova
I. V. Dolzhikova
E. I. Ermolova
M. S. Kunda
N. N. Ryzhova
O. L. Voronina
D. N. Shcherbinin
D. V. Shcheblyakov
D. Y. Logunov
A. L. Gintsburg
author_sort T. A. Ozharovskaia
collection DOAJ
description INTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophylactic vaccines requires studies aimed at selecting the most immunogenic forms of protective antigens.AIM. This study aimed to evaluate humoral immune induction in animals after administration of recombinant adenoviral vectors expressing various forms of Ebola and Marburg virus glycoproteins (GPs).MATERIALS AND METHODS. Samples of recombinant human adenovirus type 5 (rAd5) were obtained using homologous recombination in Escherichia coli, growth in HEK293 cells, and purification by CsCl gradient ultracentrifugation. The resulting rAd5 samples were characterised in terms of their identity (PCR and whole-genome sequencing), the concentration of viral particles (fluorescence spectroscopy), and the concentration of infectious viral particles (TCID50 assay). Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the GP-specific IgG titres in the sera of immunised mice.RESULTS. The authors constructed rAd5 samples, and each construct contained an expression cassette with a GP gene form encoding a full-length GP, a GP without the mucin-like domain, or a GP without both the glycan cap and the mucin-like domain. Each of these forms was studied using the GPs of four filoviruses, including Zaire Ebola virus, Sudan Ebola virus, Bundibugyo Ebola virus, and Marburg virus. Neither of the forms had a critical effect on the rAd5 replicative capacity. Three weeks after immunisation, the highest GP-specific IgG production was induced by the rAd5 samples encoding either the full-length GP or the GP without the mucin-like domain. The GP without both the glycan cap and the mucin-like domain was the least immunogenic antigen regardless of the filovirus species.CONCLUSIONS. The most promising constructs for the development of filovirus vaccines based on recombinant adenoviral vectors are the constructs that include the genes encoding the fulllength GP or the GP without the mucin-like domain.
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issn 2221-996X
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language Russian
publishDate 2024-10-01
publisher Ministry of Health of the Russian Federation. Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»
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series Биопрепараты: Профилактика, диагностика, лечение
spelling doaj-art-42d3d9ef80914aaeb81eba3135e5b8a72025-08-20T03:59:39ZrusMinistry of Health of the Russian Federation. Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»Биопрепараты: Профилактика, диагностика, лечение2221-996X2619-11562024-10-0124329431110.30895/2221-996X-2024-24-3-294-311386Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectorsT. A. Ozharovskaia0O. V. Zubkova1O. Popova2A. V. Kovyrshina3P. P. Goldovskaya4I. V. Vavilova5I. V. Dolzhikova6E. I. Ermolova7M. S. Kunda8N. N. Ryzhova9O. L. Voronina10D. N. Shcherbinin11D. V. Shcheblyakov12D. Y. Logunov13A. L. Gintsburg14National Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaNational Research Center for Epidemiology and Microbiology named after the honorary academician N. F. GamaleyaINTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophylactic vaccines requires studies aimed at selecting the most immunogenic forms of protective antigens.AIM. This study aimed to evaluate humoral immune induction in animals after administration of recombinant adenoviral vectors expressing various forms of Ebola and Marburg virus glycoproteins (GPs).MATERIALS AND METHODS. Samples of recombinant human adenovirus type 5 (rAd5) were obtained using homologous recombination in Escherichia coli, growth in HEK293 cells, and purification by CsCl gradient ultracentrifugation. The resulting rAd5 samples were characterised in terms of their identity (PCR and whole-genome sequencing), the concentration of viral particles (fluorescence spectroscopy), and the concentration of infectious viral particles (TCID50 assay). Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the GP-specific IgG titres in the sera of immunised mice.RESULTS. The authors constructed rAd5 samples, and each construct contained an expression cassette with a GP gene form encoding a full-length GP, a GP without the mucin-like domain, or a GP without both the glycan cap and the mucin-like domain. Each of these forms was studied using the GPs of four filoviruses, including Zaire Ebola virus, Sudan Ebola virus, Bundibugyo Ebola virus, and Marburg virus. Neither of the forms had a critical effect on the rAd5 replicative capacity. Three weeks after immunisation, the highest GP-specific IgG production was induced by the rAd5 samples encoding either the full-length GP or the GP without the mucin-like domain. The GP without both the glycan cap and the mucin-like domain was the least immunogenic antigen regardless of the filovirus species.CONCLUSIONS. The most promising constructs for the development of filovirus vaccines based on recombinant adenoviral vectors are the constructs that include the genes encoding the fulllength GP or the GP without the mucin-like domain.https://www.biopreparations.ru/jour/article/view/576immunogenicityglycoprotein gene variantsebola virusmarburg virushuman adenovirus type 5recombinant adenoviral vectorsebola virus diseasemarburg virus diseasehumoral immune response
spellingShingle T. A. Ozharovskaia
O. V. Zubkova
O. Popova
A. V. Kovyrshina
P. P. Goldovskaya
I. V. Vavilova
I. V. Dolzhikova
E. I. Ermolova
M. S. Kunda
N. N. Ryzhova
O. L. Voronina
D. N. Shcherbinin
D. V. Shcheblyakov
D. Y. Logunov
A. L. Gintsburg
Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors
Биопрепараты: Профилактика, диагностика, лечение
immunogenicity
glycoprotein gene variants
ebola virus
marburg virus
human adenovirus type 5
recombinant adenoviral vectors
ebola virus disease
marburg virus disease
humoral immune response
title Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors
title_full Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors
title_fullStr Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors
title_full_unstemmed Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors
title_short Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors
title_sort immunogenicity of various variants of ebola and marburg virus glycoprotein genes in recombinant adenoviral vectors
topic immunogenicity
glycoprotein gene variants
ebola virus
marburg virus
human adenovirus type 5
recombinant adenoviral vectors
ebola virus disease
marburg virus disease
humoral immune response
url https://www.biopreparations.ru/jour/article/view/576
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