Cargando…
Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®)
The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141225/ https://www.ncbi.nlm.nih.gov/pubmed/37112786 http://dx.doi.org/10.3390/vaccines11040874 |
_version_ | 1785033342091001856 |
---|---|
author | Rabdano, Sevastyan O. Ruzanova, Ellina A. Pletyukhina, Iuliia V. Saveliev, Nikita S. Kryshen, Kirill L. Katelnikova, Anastasiia E. Beltyukov, Petr P. Fakhretdinova, Liliya N. Safi, Ariana S. Rudakov, German O. Arakelov, Sergei A. Andreev, Igor V. Kofiadi, Ilya A. Khaitov, Musa R. Valenta, Rudolf Kryuchko, Daria S. Berzin, Igor A. Belozerova, Natalia S. Evtushenko, Anatoly E. Truhin, Viktor P. Skvortsova, Veronika I. |
author_facet | Rabdano, Sevastyan O. Ruzanova, Ellina A. Pletyukhina, Iuliia V. Saveliev, Nikita S. Kryshen, Kirill L. Katelnikova, Anastasiia E. Beltyukov, Petr P. Fakhretdinova, Liliya N. Safi, Ariana S. Rudakov, German O. Arakelov, Sergei A. Andreev, Igor V. Kofiadi, Ilya A. Khaitov, Musa R. Valenta, Rudolf Kryuchko, Daria S. Berzin, Igor A. Belozerova, Natalia S. Evtushenko, Anatoly E. Truhin, Viktor P. Skvortsova, Veronika I. |
author_sort | Rabdano, Sevastyan O. |
collection | PubMed |
description | The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4(+)/CD8(+) T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell(®) thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19. |
format | Online Article Text |
id | pubmed-10141225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101412252023-04-29 Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) Rabdano, Sevastyan O. Ruzanova, Ellina A. Pletyukhina, Iuliia V. Saveliev, Nikita S. Kryshen, Kirill L. Katelnikova, Anastasiia E. Beltyukov, Petr P. Fakhretdinova, Liliya N. Safi, Ariana S. Rudakov, German O. Arakelov, Sergei A. Andreev, Igor V. Kofiadi, Ilya A. Khaitov, Musa R. Valenta, Rudolf Kryuchko, Daria S. Berzin, Igor A. Belozerova, Natalia S. Evtushenko, Anatoly E. Truhin, Viktor P. Skvortsova, Veronika I. Vaccines (Basel) Article The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4(+)/CD8(+) T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell(®) thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19. MDPI 2023-04-20 /pmc/articles/PMC10141225/ /pubmed/37112786 http://dx.doi.org/10.3390/vaccines11040874 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rabdano, Sevastyan O. Ruzanova, Ellina A. Pletyukhina, Iuliia V. Saveliev, Nikita S. Kryshen, Kirill L. Katelnikova, Anastasiia E. Beltyukov, Petr P. Fakhretdinova, Liliya N. Safi, Ariana S. Rudakov, German O. Arakelov, Sergei A. Andreev, Igor V. Kofiadi, Ilya A. Khaitov, Musa R. Valenta, Rudolf Kryuchko, Daria S. Berzin, Igor A. Belozerova, Natalia S. Evtushenko, Anatoly E. Truhin, Viktor P. Skvortsova, Veronika I. Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) |
title | Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) |
title_full | Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) |
title_fullStr | Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) |
title_full_unstemmed | Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) |
title_short | Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell(®) |
title_sort | immunogenicity and in vivo protective effects of recombinant nucleocapsid-based sars-cov-2 vaccine convacell(®) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141225/ https://www.ncbi.nlm.nih.gov/pubmed/37112786 http://dx.doi.org/10.3390/vaccines11040874 |
work_keys_str_mv | AT rabdanosevastyano immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT ruzanovaellinaa immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT pletyukhinaiuliiav immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT savelievnikitas immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT kryshenkirilll immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT katelnikovaanastasiiae immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT beltyukovpetrp immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT fakhretdinovaliliyan immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT safiarianas immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT rudakovgermano immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT arakelovsergeia immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT andreevigorv immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT kofiadiilyaa immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT khaitovmusar immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT valentarudolf immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT kryuchkodarias immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT berzinigora immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT belozerovanatalias immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT evtushenkoanatolye immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT truhinviktorp immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell AT skvortsovaveronikai immunogenicityandinvivoprotectiveeffectsofrecombinantnucleocapsidbasedsarscov2vaccineconvacell |