scholarly journals Design and Synthesis of HCV-E2 Glycoprotein Epitope Mimics in Molecular Construction of Potential Synthetic Vaccines

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 326
Author(s):  
Theodorus J. Meuleman ◽  
Vanessa M. Cowton ◽  
Arvind H. Patel ◽  
Rob M. J. Liskamp
Keyword(s):  
Cyclic Peptides ◽  
Vaccine Design ◽  
Amino Acid Sequences ◽  
Direct Acting Antiviral ◽  
Design And Synthesis ◽  
E2 Glycoprotein ◽  
Highly Effective ◽  
Global Threat ◽  
Epitope Mimicry ◽  
Hcv E2 Glycoprotein

Hepatitis C virus remains a global threat, despite the availability of highly effective direct-acting antiviral (DAA) drugs. With thousands of new infections annually, the need for a prophylactic vaccine is evident. However, traditional vaccine design has been unable to provide effective vaccines so far. Therefore, alternative strategies need to be investigated. In this work, a chemistry-based approach is explored towards fully synthetic peptide-based vaccines using epitope mimicry, by focusing on highly effective and conserved amino acid sequences in HCV, which, upon antibody binding, inhibit its bio-activity. Continuous and discontinuous epitope mimics were both chemically synthesized based on the HCV-E2 glycoprotein while using designed fully synthetic cyclic peptides. These cyclic epitope mimics were assembled on an orthogonally protected scaffold. The scaffolded epitope mimics have been assessed in immunization experiments to investigate the elicitation of anti-HCV-E2 glycoprotein antibodies. The neutralizing potential of the elicited antibodies was investigated, representing a first step in employing chemically synthesized epitope mimics as a novel strategy towards vaccine design.

scholarly journals Immunogenicity of NS4b Dengue 3 Virus Mimotope Presented to the Immune System as Multiple Antigen Peptide System

ISRN Virology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Nevis Amin ◽  
Maritza Pupo ◽  
Alicia Aguilar ◽  
Frank Camacho ◽  
Mayling Alvarez ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Vaccine Design ◽  
Amino Acid Sequences ◽  
Diagnostic Assays ◽  
Random Peptide ◽  
Multiple Antigen ◽  
Antigen Peptide ◽  
Multiple Antigen Peptide ◽  
Human Sera ◽  
Phage Displayed Peptide Library

The availability of random peptide libraries displayed on bacteriophage (RPL) has provided a powerful tool for selecting sequences that mimic binding properties of natural antigen epitopes (mimotopes). These mimotopes can be used for vaccine design, drug development, and diagnostic assays. Several mimotopes have been shown to induce production of antibodies against the natural antigen. We have previously identified four dengue virus mimotopes from a phage-displayed peptide library using antidengue 3 human sera. Three of them showed similarity in their amino acid sequences with the NS4b proteins of dengue. Few studies have examined the role of NS4b proteins in the antibody response to dengue virus infection. A multiple antigen peptide (MAP) system was chemically synthesized containing this mimotope (NS4b MAP), and BALB/c mice were immunized to evaluate its immunogenicity. Antipeptide responses were induced and recognised DENV-3 infected cells as determined by immunofluorescence. The high levels of the IgG2a subtype against NS4bMAP suggest the induction of a Th1-like response. Our findings suggest that the NS4b mimotope might be a useful tool for the development of multiepitope diagnostic assays, dengue virus vaccine design, and pathogenesis studies.

Sialylation of HCV E2 Glycoprotein-Specific and Natural Anti-Glycan (TF, αGal) Antibodies as Signatures of Liver Damage

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kurtenkov O ◽  
◽  
Jakovleva J ◽  
Sergejev B ◽  
Geller J ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Liver Damage ◽  
Hepatic Damage ◽  
High Rate ◽  
Specific Antibodies ◽  
Non Invasive ◽  
E2 Glycoprotein ◽  
Invasive Evaluation ◽  
Hcv E2 Glycoprotein

The E2 glycoprotein is the target of broadly neutralizing antibodies against Hepatitis C Virus (HCV). There is evidence that the HCV E2-specific antibody glycosylation profile is associated with hepatic fibrosis progression. The main aim of this study was to compare the sialylation of E2-specific and naturally occurring antiglycan Abs to determine whether their combination could be beneficial for the non-invasive evaluation of hepatic damage. Fifty-eight patients with various stages of hepatic fibrosis or without were tested. The sialylation of HCV E2 glycoprotein-specific antibodies (E2-Abs), the Thomsen-Friedenreich antigen- and αGal glycotope-specific antibodies (TF-Abs, αGal-Abs) was analysed using the ELISA platform. The level of IgG Abs and their reactivity to Sialospecific Sambucus Nigra Lectin (SNA) were determined and changes in Abs sialylation were analysed based on the stage of liver fibrosis, HCV genotype and antiviral therapy efficacy. The late stage of liver Fibrosis (F4) was characterized by dramatically decreased E2-Ab SNA reactivity unlike stages with no fibrosis (P=0.003) and stages F1–F3 (P=0.0007). In contrast, antiglycan Abs showed an increased sialylation. In multiple regression analysis, the combination of E2 and TF-Abs sialylation patterns gave a significant advantage in assessing liver damage. A high rate of discrimination between F0 and F4 stages of fibrosis as well as between F1–F3 and F4 was obtained (ACC=0.948 and ACC=0.90, respectively). Thus, the combined analysis of disease-specific and natural Abs sialylation can remarkably enhance the clinical value of the approach in the non-invasive evaluation of hepatic damage.

scholarly journals Design and Synthesis of Highly-Dispersed WO3 Catalyst with Highly Effective NH3–SCR Activity for NOx Abatement

ACS Catalysis ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 11557-11562 ◽  
Author(s):  
Haidi Xu ◽  
Jixing Liu ◽  
Zihao Zhang ◽  
Shuang Liu ◽  
Qinjing Lin ◽  
...  
Keyword(s):  
Design And Synthesis ◽  
Nox Abatement ◽  
Nh3 Scr ◽  
Highly Dispersed ◽  
Highly Effective

FRI-388-Hepatitis C ilnfected liver grafts transplanted into non-infected recipients are safe in the era of highly effective direct-acting antiviral therapy

2019 ◽  
Vol 70 (1) ◽  
pp. e565-e566
Author(s):  
Heather O’dell ◽  
Alison Rafferty ◽  
Natasha Schneider ◽  
Andrew Scanga ◽  
J. Kelly Wright ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Direct Acting Antiviral ◽  
Highly Effective ◽  
Direct Acting

Molecular Design and Synthesis of Artificial Ion Channels Based on Cyclic Peptides Containing Unnatural Amino Acids

2001 ◽  
Vol 66 (9) ◽  
pp. 2978-2989 ◽  
Author(s):  
Hitoshi Ishida ◽  
Zhi Qi ◽  
Masahiro Sokabe ◽  
Kiyoshi Donowaki ◽  
Yoshihisa Inoue
Keyword(s):  
Amino Acids ◽  
Ion Channels ◽  
Unnatural Amino Acids ◽  
Cyclic Peptides ◽  
Molecular Design ◽  
Design And Synthesis

scholarly journals Design and Synthesis of C-Terminal Modified Cyclic Peptides as VEGFR1 Antagonists

Molecules ◽  
2014 ◽  
Vol 19 (10) ◽  
pp. 15391-15407 ◽  
Author(s):  
Lei Wang ◽  
Nathalie Gagey-Eilstein ◽  
Sylvain Broussy ◽  
Marie Reille-Seroussi ◽  
Florent Huguenot ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Design And Synthesis

Molecular study and epitope mapping of the human antibody response against HCV/E2 glycoprotein by generation of monoclonal recombinant Fabs

2000 ◽  
Vol 118 (4) ◽  
pp. A1016
Author(s):  
Crsitiana Di Campli ◽  
Roberto Burioni ◽  
Francesca Bugli ◽  
Alessandra Desogus ◽  
Alessandro Vannini ◽  
...  
Keyword(s):  
Antibody Response ◽  
Epitope Mapping ◽  
Molecular Study ◽  
Human Antibody ◽  
E2 Glycoprotein ◽  
Hcv E2 Glycoprotein
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