Mapping of B-cell epitopes on the N- terminal and C-terminal segment of nucleocapsid protein from Crimean-Congo hemorrhagic fever virus

Moming, Abulimiti; Tuoken, Daerken; Yue, Xihong; Xu, Wan-Xiang; Guo, Rong; Liu, Dongliang; Li, Yijie; Hú, Zhìhóng; Deng, Fei; Zhāng, Yújiāng; Sun, Song

doi:10.1371/journal.pone.0204264

Cited by 19 publications

(18 citation statements)

References 41 publications

(55 reference statements)

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“…The protein is produced in large amounts during infection and is highly immunogenic containing B and T cell epitopes. 86,87 Besides that, the NP amino acid sequence shows the least variation 88 thus, an NP-based vaccine is expected to offer protection against the diverse CCHFV strains. Recently, complete protection in knockout mice against CCHFV challenge infection has been reported after vaccination with NP-based vaccines using different expression systems.…”

Section: Nucleoproteinmentioning

confidence: 99%

Crimean–Congo Hemorrhagic Fever Virus: Advances in Vaccine Development

Tipih

Burt

2020

BioResearch Open Access

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Crimean-Congo hemorrhagic fever (CCHF) is a severe human disease with mortality rates of up to 30%. The disease is widespread in Africa, Asia, the Middle East and Eastern Europe. The last few years have seen disease emergence in Spain for the first time and disease re-emergence in other regions of the world after periods of inactivity. Factors, such as climate change, movement of infected ticks, animals, and changes in human activity, are likely to broaden endemic foci. There are therefore concerns that CCHF might emerge in currently nonendemic regions. The absence of approved vaccines or therapies heightens these concerns; thus Crimean-Congo hemorrhagic fever virus (CCHFV) is listed by the World Health Organization as a priority organism. However, the current sporadic nature of CCHF cases may call for targeted vaccination of risk groups as opposed to mass vaccinations. CCHF vaccine development has accelerated in recent years, partly because of the discovery of CCHF animal models. In this review, we discuss CCHF risk groups who are most likely to benefit from vaccine development, the merits and demerits of available CCHF animal models, and the various approaches which have been explored for CCHF vaccine development. Lastly, we present concluding remarks and research areas which can be further explored to enhance the available CCHFV vaccine data.

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Section: Nucleoproteinmentioning

confidence: 99%

Crimean–Congo Hemorrhagic Fever Virus: Advances in Vaccine Development

Tipih

Burt

2020

BioResearch Open Access

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“…It is a common phenomenon for many species studied; for instance, the sheep serum to peste des petits ruminants virus (PPRV) could recognize 9 of 13 BCEs on hemagglutinin (H) protein of PPRV [36], and the murine pAbs to HPV58 L1-VLP could react with 13 of 18 BCEs mapped by rabbit pAbs to r-HPV58-L1 [24]. Notably, the completely similar antibody-responses to a given antigen also existed between various species sometimes; for instance, all rabbit IgG-BCEs on NPs of CCHFV/PPRV could react with the antisera from sheep CCHFV or PPRV-infected [25, 37], and the antibodies to three of β-hCG BCEs present in a chimeric peptide immunogen all were generated in both rabbit and mice [38]. These results indicate that the immune systems of rabbit, murine and sheep could recognize most and/or all of antigenic sites present in a given antigen despite differing greatly in biology and genetics for them, and thus can explain why there are too many reports on identifying BCEs on various viral proteins with rabbit and mouse antisera.…”

Section: Discussionmentioning

confidence: 99%

“…Xu et al have used their own developed method to identify many fine BCEs on human zona pellucida glycoprotein-3 (hZP3) and human hZP4 using rabbit pAbs [21, 23], and especially to reveal three fine rabbit IgG-epitomes of human papilloma virus type 58 (HPV58) E6, E7 and L1 proteins for the first time [24]. In our previous studies, a lot of fine BCEs on the Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP) and Gn were identified also using the method [25, 26], of which all the identified BCEs were recognized by anti-CCHFV positive sheep serum, confirming that the BSP method is credible and easy to operate for epitope mapping.…”

Section: Introductionmentioning

confidence: 99%

Fine epitope mapping of glycoprotein Gn in Guertu virus

et al. 2019

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Guertu virus (GTV) is a tick-borne phleboviruses (TBPVs) which belongs to the genus Banyangvirus in the family of Phenuiviridae. In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice. Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein. The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn. Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are EGn1 (), EGn2 (), EGn3 (), EGn4 (), EGn5 (), EGn6 (), EGn7 (), AP-8 () and AP-9 (), of which six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally. Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV. The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen.

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“…Nucleoproteins and glycoproteins are two major structural proteins of CCHFV, and play a key role in the viral infection process. Nucleoprotein NP is the main antigen that induces humoral and cellular immunity in the body [28]. The mature glycoprotein GP is very important in the process of virus infection and pathogenicity, and can induce neutralizing antibodies.…”

Section: Discussionmentioning

confidence: 99%

Immune responses in mice induced by multi-epitope DNA vaccine and protein vaccine of Crimean-Congo Hemorrhagic Fever Virus

Sun

Yusufu

Shalitanati

et al. 2019

Preprint

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Crimean-Congo Hemorrhagic Fever (CCHF), caused by the CCHF virus (CCHFV), is a severe tick borne zoonosis widely distributed in over 30 countries and regions. Currently, there is no licensed vaccine available for CCHF in China. To evaluate the cellular and humoral immune responses induced by multi-epitope DNA and protein vaccine of CCHF in BALB/c mice, a multi-epitope gene (MEPX) segment with tandem including six highly conservative and immunedominant B cell epitopes was designed based on the analysis of hydrophilicity and antigenic determinant sites in amino acid sequences of nucleoprotein and glycoprotein from CCHFV strain YL04057. The single and doublecopy multi-epitope gene (MEPX and MEPX 2 ) were respectively cloned into the eukaryotic expression vector pVAX I to construct the recombinant (r) plasmid pVAX-MEPX and pVAX-MEPX 2 as DNA vaccines. The results of immunofluorescence in vitro showed that the pVAX-MEPX and pVAX-MEPX 2 could be expressed in 293T cells. The recombinant prokaryotic plasmid pET-32a-MEPX and pET-32a-MEPX 2 constructed previously were transformed them into E. coli BL21 (DE3), and recombinant multiepitope proteins (rMEPX and rMEPX 2 ) were obtained and purificated by Nickel affinity chromatography. Western blot results showed that rMEPX and rMEPX 2 had good antigenicity. BALB/c mice were immunized with DNA vaccine alone, protein vaccine alone, and DNA prime followed by recombinant protein boost immunization strategy, respectively. After three immunizations, MTT assay, cytokine content assay, and ELISA assay for antibody titers were used to evaluate the immune response. The proliferation of mouse specific T lymphocytes in the enhanced by pVAX-MEPX 2 combined with rMEPX 2 boosting group was significant, and the expression levels of serum IFN-γ and IL-4 in mice were as high as 118.67 pg/mL and 135.33 pg/mL with significant difference compared to the control group (p<0.01), and serum antibody titer could reach up to 4.1×10 5 . Double-copy multi-epitope vaccines groups (pVAX-MEPX 2 + rMEPX 2 ) generated better cellular and humoral immune responses by DNA prime-protein vaccine boost combinatorial immunization. This result could lay the foundation for the development of CCHFV multi-epitope vaccine candidates.

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Mapping of B-cell epitopes on the N- terminal and C-terminal segment of nucleocapsid protein from Crimean-Congo hemorrhagic fever virus

Cited by 19 publications

References 41 publications

Crimean–Congo Hemorrhagic Fever Virus: Advances in Vaccine Development

Crimean–Congo Hemorrhagic Fever Virus: Advances in Vaccine Development

Fine epitope mapping of glycoprotein Gn in Guertu virus

Immune responses in mice induced by multi-epitope DNA vaccine and protein vaccine of Crimean-Congo Hemorrhagic Fever Virus

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