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GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice
The Crimean Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne bunyavirus of the Narovirus genus, which is the causative agent of Crimean Congo Hemorrhagic Fever (CCHF). CCHF is endemic in Africa, the Middle East, Eastern Europe and Asia, with a high case-fatality rate of up to 50% in humans. Cur...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416392/ https://www.ncbi.nlm.nih.gov/pubmed/36016285 http://dx.doi.org/10.3390/v14081664 |
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author | Wang, Qi Wang, Shen Shi, Zhikang Li, Zhengrong Zhao, Yongkun Feng, Na Bi, Jinhao Jiao, Cuicui Li, Entao Wang, Tiecheng Wang, Jianzhong Jin, Hongli Huang, Pei Yan, Feihu Yang, Songtao Xia, Xianzhu |
author_facet | Wang, Qi Wang, Shen Shi, Zhikang Li, Zhengrong Zhao, Yongkun Feng, Na Bi, Jinhao Jiao, Cuicui Li, Entao Wang, Tiecheng Wang, Jianzhong Jin, Hongli Huang, Pei Yan, Feihu Yang, Songtao Xia, Xianzhu |
author_sort | Wang, Qi |
collection | PubMed |
description | The Crimean Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne bunyavirus of the Narovirus genus, which is the causative agent of Crimean Congo Hemorrhagic Fever (CCHF). CCHF is endemic in Africa, the Middle East, Eastern Europe and Asia, with a high case-fatality rate of up to 50% in humans. Currently, there are no approved vaccines or effective therapies available for CCHF. The GEM-PA is a safe, versatile and effective carrier system, which offers a cost-efficient, high-throughput platform for recovery and purification of subunit proteins for vaccines. In the present study, based on a GEM-PA surface display system, a GEM-PA based vaccine expressing three subunit vaccine candidates (G-GP, including G-eG(N), G-eG(C) and G-NAb) of CCHFV was developed, displaying the ectodomains of the structural glycoproteins eG(N), eG(C) and NAb, respectively. According to the immunological assays including indirect-ELISA, a micro-neutralization test of pseudo-virus and ELISpot, 5 μg GPBLP(3) combined with Montanide ISA 201VG plus Poly (I:C) adjuvant (A-G-GP-5 μg) elicited GP-specific humoral and cellular immunity in BALB/c mice after three vaccinations via subcutaneous injection (s.c.). The consistent data between IgG subtype and cytokine detection, ELISpot and cytokine detection indicated balanced Th1 and Th2 responses, of which G-eG(N) vaccines could elicit a stronger T-cell response post-vaccination, respectively. Moreover, all three vaccine candidates elicited high TNF-α, IL-6, and IL-10 cytokine levels in the supernatant of stimulated splenocytes in vitro. However, the neutralizing antibody (nAb) was only detected in A-G-eG(C) and A-G-eG(C) vaccination groups with the highest neutralizing titer of 128, suggesting that G-eG(C) could elicit a stronger humoral immune response. In conclusion, the GEM-PA surface display system could provide an efficient and convenient purification method for CCHFV subunit antigens, and the G-GP subunit vaccine candidates will be promising against CCHFV infections with excellent immunogenicity. |
format | Online Article Text |
id | pubmed-9416392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94163922022-08-27 GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice Wang, Qi Wang, Shen Shi, Zhikang Li, Zhengrong Zhao, Yongkun Feng, Na Bi, Jinhao Jiao, Cuicui Li, Entao Wang, Tiecheng Wang, Jianzhong Jin, Hongli Huang, Pei Yan, Feihu Yang, Songtao Xia, Xianzhu Viruses Article The Crimean Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne bunyavirus of the Narovirus genus, which is the causative agent of Crimean Congo Hemorrhagic Fever (CCHF). CCHF is endemic in Africa, the Middle East, Eastern Europe and Asia, with a high case-fatality rate of up to 50% in humans. Currently, there are no approved vaccines or effective therapies available for CCHF. The GEM-PA is a safe, versatile and effective carrier system, which offers a cost-efficient, high-throughput platform for recovery and purification of subunit proteins for vaccines. In the present study, based on a GEM-PA surface display system, a GEM-PA based vaccine expressing three subunit vaccine candidates (G-GP, including G-eG(N), G-eG(C) and G-NAb) of CCHFV was developed, displaying the ectodomains of the structural glycoproteins eG(N), eG(C) and NAb, respectively. According to the immunological assays including indirect-ELISA, a micro-neutralization test of pseudo-virus and ELISpot, 5 μg GPBLP(3) combined with Montanide ISA 201VG plus Poly (I:C) adjuvant (A-G-GP-5 μg) elicited GP-specific humoral and cellular immunity in BALB/c mice after three vaccinations via subcutaneous injection (s.c.). The consistent data between IgG subtype and cytokine detection, ELISpot and cytokine detection indicated balanced Th1 and Th2 responses, of which G-eG(N) vaccines could elicit a stronger T-cell response post-vaccination, respectively. Moreover, all three vaccine candidates elicited high TNF-α, IL-6, and IL-10 cytokine levels in the supernatant of stimulated splenocytes in vitro. However, the neutralizing antibody (nAb) was only detected in A-G-eG(C) and A-G-eG(C) vaccination groups with the highest neutralizing titer of 128, suggesting that G-eG(C) could elicit a stronger humoral immune response. In conclusion, the GEM-PA surface display system could provide an efficient and convenient purification method for CCHFV subunit antigens, and the G-GP subunit vaccine candidates will be promising against CCHFV infections with excellent immunogenicity. MDPI 2022-07-28 /pmc/articles/PMC9416392/ /pubmed/36016285 http://dx.doi.org/10.3390/v14081664 Text en © 2022 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 Wang, Qi Wang, Shen Shi, Zhikang Li, Zhengrong Zhao, Yongkun Feng, Na Bi, Jinhao Jiao, Cuicui Li, Entao Wang, Tiecheng Wang, Jianzhong Jin, Hongli Huang, Pei Yan, Feihu Yang, Songtao Xia, Xianzhu GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice |
title | GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice |
title_full | GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice |
title_fullStr | GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice |
title_full_unstemmed | GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice |
title_short | GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice |
title_sort | gem-pa-based subunit vaccines of crimean congo hemorrhagic fever induces systemic immune responses in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416392/ https://www.ncbi.nlm.nih.gov/pubmed/36016285 http://dx.doi.org/10.3390/v14081664 |
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