Unravelling viral camouflage: approaches to the study and characterization of conformational epitopes

Augustin, Teresa L.; Cehlár, Ondrej; Škrabana, Rostislav; Majerová, Petra; Hanes, Jozef

doi:10.4149/av_2015_02_103

Cited by 8 publications

(3 citation statements)

References 114 publications

(138 reference statements)

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“…Epitopes were initially identified in foot-and-mouth disease viruses ( 28 ). Epitopes are divided into conformational epitopes and linear epitopes based on their structure and they are also divided into B-cell epitopes and T-cell epitopes when present on different receptor-binding cells ( 29 – 32 ). Linear epitopes are primarily recognized by T-cell antigen receptors and they are also recognized by B-cell antigen receptors, while conformational epitopes are only recognized by B-cell antigen receptors ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Expression of vitamin D receptor in bronchial asthma and its bioinformatics prediction

et al. 2018

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Vitamin D receptors (VDRs) are associated with the occurrence and development of asthma. The aim of the present study was to analyze the secondary structure and B-cell and T-cell epitopes of VDR using online prediction software and aid in the future development of a highly efficient epitope-based vaccine against asthma. Blood samples were collected from peripheral blood of asthmatic children. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was performed to detect the expression of VDR in the peripheral blood. Mouse models of asthma were established. Hematoxylin and eosin staining was performed to observe the pathological alterations of the lungs of mice. Immunohistochemistry, western blot analysis and RT-qPCR were performed to detect the expression of VDR in the lungs of asthmatic mice. Online prediction software immune epitope database and analysis resource, SYFPEITHI and linear epitope prediction based on propensity scale and support vector machines were used to predict the B-cell and T-cell epitopes and the RasMol and 3DLigandSite were used to analyze the tertiary structure of VDR. RT-qPCR demonstrated that VDR expression in the peripheral blood of asthmatic children was decreased. Immunohistochemistry, western blotting and RT-qPCR demonstrated that VDR expression also decreased in the lungs of mouse models of asthma. VDR B-cell epitopes were identified at 37–45, 88–94, 123–131, 231–239, 286–294 and 342–350 positions of the amino acid sequence and VDR T-cell epitopes were identified at 125–130, 231–239 and 265–272 positions. A total of six B-cell epitopes and three T-cell epitopes for VDR were predicted by bioinformatics, which when validated, may in the future aid in immunological diagnosis and development of a targeted drug therapy for clinical asthma.

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Section: Discussionmentioning

confidence: 99%

Expression of vitamin D receptor in bronchial asthma and its bioinformatics prediction

et al. 2018

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“…In nature coiled-coils exist that consist of 2, 3, 4, 5, and 6 a-helices while 7 membered coiledcoil domains have been synthesized in the laboratory [191]. B-cell epitopes can be conformational, meaning the epitope is based on the structure of the antigen, not the linear sequence [192]. The toolbox of well-established well-understood coiled-coil oligomerization domains allows for the presentation of antigens, in particular for oligomeric antigens, in their native conformations.…”

Section: Rationally Designed Protein Nanovaccinesmentioning

confidence: 99%

Vaccine technologies: From whole organisms to rationally designed protein assemblies

Karch¹,

Burkhard²

2016

Biochemical Pharmacology

215

185

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Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development.

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“…Furthermore, SAPN offer the possibility to customize display on both the N-and C-termini to gain a more native-like, unconstrained structure, allowing conformational epitopes to form. In the same way, linear T-cell epitopes can be incorporated in the coiled-coil core sequence to activate both cellular and humoral immune responses [56]. In contrast to multiple antigenic peptides (MAP) [57,58], the production of SAPN vaccines is relatively robust, efficient, and cost-reductive.…”

Section: Introductionmentioning

confidence: 99%

Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity

et al. 2021

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Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled particle and are aspects to consider for a rationally designed effective vaccine. Here, we characterize the folding and immunogenicity of heterogeneous antigen display by integrating (a) dual-stage antigen SAPN presenting the P. falciparum (Pf) merozoite surface protein 1 subunit, PfMSP119, and Pf cell-traversal protein for ookinetes and sporozoites, PfCelTOS, in addition to (b) a homogenous antigen SAPN displaying two copies of PfCelTOS. Mice and rabbits were utilized to evaluate antigen-specific humoral and cellular induction as well as functional antibodies via growth inhibition of the blood-stage parasite. We demonstrate that antigen orientation and folding influence the elicited immune response, and when appropriately designed, SAPN can serve as an adaptable platform for an effective multi-antigen display.

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Unravelling viral camouflage: approaches to the study and characterization of conformational epitopes

Cited by 8 publications

References 114 publications

Expression of vitamin D receptor in bronchial asthma and its bioinformatics prediction

Expression of vitamin D receptor in bronchial asthma and its bioinformatics prediction

Vaccine technologies: From whole organisms to rationally designed protein assemblies

Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity

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