scholarly journals Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice

2018 ◽  
Vol 140 (48) ◽  
pp. 16596-16609 ◽  
Author(s):  
Xuanjun Wu ◽  
Zhaojun Yin ◽  
Craig McKay ◽  
Christian Pett ◽  
Jin Yu ◽  
...  

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 270
Author(s):  
Nicky de Vrij ◽  
Pieter Meysman ◽  
Sofie Gielis ◽  
Wim Adriaensen ◽  
Kris Laukens ◽  
...  

Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.



2018 ◽  
Vol 9 ◽  
Author(s):  
Clarisa Beatriz Palatnik-de-Sousa ◽  
Irene da Silva Soares ◽  
Daniela Santoro Rosa


2016 ◽  
Vol 22 (10) ◽  
pp. 1192-1192 ◽  
Author(s):  
Carsten Linnemann ◽  
Marit M van Buuren ◽  
Laura Bies ◽  
Els M E Verdegaal ◽  
Remko Schotte ◽  
...  


2015 ◽  
Vol 9 (7) ◽  
pp. e0003917 ◽  
Author(s):  
Arnone Nithichanon ◽  
Darawan Rinchai ◽  
Alessandro Gori ◽  
Patricia Lassaux ◽  
Claudio Peri ◽  
...  


Rheumatology ◽  
2019 ◽  
Author(s):  
Martial Koenig ◽  
Chelsea Bentow ◽  
Minoru Satoh ◽  
Marvin J Fritzler ◽  
Jean-Luc Senécal ◽  
...  

Abstract Objective Detection of antinuclear antibodies and specific autoantibodies is important in the diagnosis and classification of SSc. Several proteins of the Th/To complex, including Rpp25, Rpp38 and hPop1 are the target of autoantibodies in SSc patients. However, very little is known about the epitope distribution of this autoantigen. Consequently, we screened Rpp25, Rpp38 and hPop1 for B cell epitopes and evaluated their clinical relevance. Methods Serum pools with (n = 2) and without (n = 1) anti-Th/To autoantibodies were generated and used for epitope discovery. Identified biomarker candidate sequences were then utilized to synthesize synthetic, biotinylated, soluble peptides. The peptides were tested to determine reactivity with sera from SSc cohorts (n = 202) and controls (n = 159) using a chemiluminescence immunoassay. Additionally, samples were also tested for antibodies to full-length recombinant Rpp25 antibodies by chemiluminescence immunoassay. Results Several immunodominant regions were found on the three proteins. The strongest reactivity was observed with an Rpp38 peptide (aa 229–243). Autoantibodies to the Rpp38 peptide were detected in 8/149 (5.4%) limited cutaneous SSc patients, but not in any of 159 controls (P = 0.003 by two-sided Fisher's exact probability test). Although reactivity to the novel antigenic peptide was correlated with the binding to Rpp25 (rho = 0.44; P < 0.0001), subsets of patient sera either reacted strongly with Rpp25 or with the novel Rpp38-derived peptide. Conclusion A novel Rpp38 epitope holds promise to increase the sensitivity in the detection of anti-Th/To autoantibodies, thus enhancing the serological diagnosis of SSc.



2020 ◽  
Author(s):  
Daniel W. Biner ◽  
Jason S. Grosch ◽  
Peter J. Ortoleva

<p></p><p>Antibody-antigen interaction – at antigenic local environments called B-cell epitopes – is a prominent mechanism for neutralization of infection. Effective mimicry, and display, of B-cell epitopes is key to vaccine design. Here, a physical approach is evaluated for the discovery of epitopes which evolve slowly over closely related pathogens (conserved epitopes). The approach is 1) protein flexibility-based and 2) demonstrated with clinically relevant enveloped viruses, simulated via molecular dynamics. The approach is validated against 1) seven structurally characterized enveloped virus epitopes which evolved the least (out of thirty-eight enveloped virus-antibody structures) and 2) eight preexisting epitope and peptide discovery algorithms. Rationale for a new benchmarking scheme is presented. A data-driven epitope clustering algorithm is introduced. The prediction of eleven Zika virus epitopes (for future exploration on recombinant vaccine technologies) is demonstrated. For the first time, protein flexibility is shown to outperform solvent accessible surface area as an epitope discovery metric.</p><p></p>



2021 ◽  
Vol 15 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee

: Coronavirus Disease 2019 (COVID-19) is caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is the most challenging pandemic of this century. The growing COVID-19 pandemic has triggered extraordinary efforts to restrict the virus in numerous ways, owing to the emergence of SARS-CoV-2. Immunotherapy, which includes artificially stimulating the immune system to generate an immunological response, is regarded as an effective strategy for preventing and treating several infectious illnesses and malignancies. Given the pandemic's high fatality rate and quick expansion, an effective vaccination is urgently needed to keep it under control. The basic goal of all COVID-19 vaccine programs is to develop a vaccine that causes the generation of surface protein neutralizing antibodies in subjects. The epitope discovery for the SARS-CoV-2 vaccine candidates is likewise made using an immuno-informatics methodology. It can be used to find the epitopes in viral proteins important for cytotoxic T cells and B cells. A safe and effective COVID-19 vaccine that can elicit the necessary immune response is necessary to end the epidemic. The global search for a safe and effective COVID-19 vaccine is yielding results. More than a dozen vaccines have already been approved around the world, with many more in the clinical trials. Patents can cover the underlying technology used to generate a vaccine, whereas trade secrets can cover manufacturing methods and procedures.



2020 ◽  
Vol 3 (1) ◽  
pp. 191-215 ◽  
Author(s):  
Morten Nielsen ◽  
Massimo Andreatta ◽  
Bjoern Peters ◽  
Søren Buus

Immunoinformatics is a discipline that applies methods of computer science to study and model the immune system. A fundamental question addressed by immunoinformatics is how to understand the rules of antigen presentation by MHC molecules to T cells, a process that is central to adaptive immune responses to infections and cancer. In the modern era of personalized medicine, the ability to model and predict which antigens can be presented by MHC is key to manipulating the immune system and designing strategies for therapeutic intervention. Since the MHC is both polygenic and extremely polymorphic, each individual possesses a personalized set of MHC molecules with different peptide-binding specificities, and collectively they present a unique individualized peptide imprint of the ongoing protein metabolism. Mapping all MHC allotypes is an enormous undertaking that cannot be achieved without a strong bioinformatics component. Computational tools for the prediction of peptide–MHC binding have thus become essential in most pipelines for T cell epitope discovery and an inescapable component of vaccine and cancer research. Here, we describe the development of several such tools, from pioneering efforts to the current state-of-the-art methods, that have allowed for accurate predictions of peptide binding of all MHC molecules, even including those that have not yet been characterized experimentally.



2000 ◽  
Vol 31 (4) ◽  
pp. S309-S310
Author(s):  
Helen Melzer ◽  
Franco Felici ◽  
Erfan Mansouri ◽  
Paola Fortugno ◽  
Alexandra Marinets ◽  
...  


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