Home » Publications

Publications

Discover how PEPperPRINT Peptide Microarray products have been used in different fields of research.

Compounds and Methods Targeting Interleukin-19

Higgs Jr., Richard Earl; Konrad, Robert John; Nickoloff, Brian Jeffrey; Siegel II, Robert William; Mertz, Prema Maria
Nov 2020
The present invention provides compounds and methods targeting human interleukin-19, including therapeutic antibodies, pharmaceutical compositions and diagnostic applications useful in the field of immune-mediated diseases including psoriasis, atopic dermatitis, psoriatic arthritis, bronchial asthma and diabetic nephropathy.

Ns2b as Marker for Zika Virus Infections

Jaenisch, Thomas; Fischer, Nico; Loeffler, Felix; Sekul, Renate; Stadler, Volker; Marques, Ernesto T. A.; Lucas, Zachariah
Oct 2020
The present invention relates to protein NS2b or fragment(s) thereof as biomarker or diagnostic marker for the diagnosis and/or prognosis of Zika virus infections. The present invention further relates to peptides and cyclic peptides, compositions and arrays and multimer compounds comprising them. The present invention further relates to a method for the diagnosis and/or prognosis of Zika virus infections, comprising the use of protein NS2b or fragment(s) thereof, or of the peptides, cyclic peptides, compositions and/or arrays in immunoassays. The present invention further relates to peptide-based compounds comprising at least one fragment of protein NS2b and at least one further component and to methods for the diagnosis and/or prognosis of Zika virus infections.

Monoclonal Antibodies to Growth and Differentiation Factor 15 (gdf-15), and Uses Thereof for Treating Cancer Cachexia and Cancer

Wischhusen, Jörg; Junker, Markus; Schäfer, Tina; Pühringer, Dirk; Lucas, Zachariah
Oct 2020
The present invention relates to monoclonal anti-human-GDF-15 antibodies. The antibodies include chimeric anti-bodies and humanized antibodies. The invention also relates to monoclonal anti-human-GDF-15 antibodies including murine anti-bodies, chimeric antibodies and humanized antibodies for use in methods for the treatment of cancer cachexia and also for the treatment of cancer. The invention also provides pharmaceutical compositions, kits, methods and uses and cell lines capable of producing the monoclonal antibodies of the invention.

Detection of specific IgE against linear epitopes from Gal d 1 has additional value in diagnosing hen’s egg allergy in adults

Ehlers, Anna M.; Otten, Henny G.; Wierzba, Eva; Flügge, Ulrike; Le, Thuy-My; Knulst, André C.; Suer, Waltraud
Background Although hen’s egg allergy is more prevalent in children, up to 0.6% of adults from different European countries suffers from a persistent or newly-onset hen’s egg allergy, making accurate diagnosis in adults necessary. However, sensitisation to hen’s egg extracts, components and linear epitopes are solely studied in children. Methods Hen’s egg allergic (n=16) and tolerant (n=20) adults were selected by sensitisation towards recombinant components rGal d 1 and/or 3. Sensitisation profiles towards egg white and yolk extract and the native components Gal d 1, 2, 3 and 4 were respectively evaluated with the ImmunoCAP or the EUROLINE system. Characterisation of linear epitopes was performed with a peptide microarray containing 15mer peptides representing the entire sequence of mature Gal d 1 and 3. Results Overall, sIgE titres against hen’s egg extracts and single components overlapped largely between allergic and tolerant adults. Although the median sIgE/sIgG4 ratio to Gal d 1 was increased in allergic adults, the range was comparable between both groups. Clinically relevant sensitisation to Gal d 1 was confirmed by sIgE-binding to the linear epitopes aa30-41, aa39-50 or aa84-95 in 6/13 allergic adults, mainly suffering from objective symptoms. In comparison, these epitopes were recognized by 1/15 tolerant patient. Only a few linear epitopes were detected for Gal d 3, suggesting a greater importance of conformational epitopes for the recognition of Gal d 3. Conclusion and Clinical Relevance Specific IgE-binding to linear epitopes of Gal d 1 is highly specific in identifying hen’s egg allergic adults with objective symptoms.

Rapid response to pandemic threats: immunogenic epitope detection of pandemic pathogens for diagnostics and vaccine development using peptide microarrays

Heiss, Kirsten; Heidepriem, Jasmin; Fischer, Nico; Weber, Laura K; Dahlke, Christine; Jaenisch, Thomas; Loeffler, Felix F
J. Proteome Res..
Sep 2020
Emergence and re-emergence of pathogens bearing the risk of becoming a pandemic threat are on the rise. Increased travel and trade, growing population density, changes in urbanization, and climate have a critical impact on infectious disease spread. Currently, the world is confronted with the emergence of a novel coronavirus SARS-CoV-2, responsible for yet more than 500 000 deaths globally. Outbreaks caused by viruses such as SARS-CoV-2, HIV, Ebola, influenza, and Zika have increased over the last decade, underlining the urgent need for a rapid development of diagnostics and vaccines. Hence, the rational identification of biomarkers for diagnostic measures on the one hand, and antigenic targets for vaccine development on the other, are of utmost importance. Peptide microarrays can display large numbers of putative target proteins translated into overlapping linear (and cyclic) peptides. Using these highly diverse libraries, covering tens of thousands of peptides, allow for the in-depth analysis of antibody signatures in a multiplexed, high-throughput fashion. In this review, we highlight synthesis platforms that facilitate fast and highly flexible generation of high-density peptide microarrays. We further outline the multifaceted applications of these peptide array platforms for the development of serological tests and vaccines, to quickly encounter pandemic threats.

Molecular and Serological Tests for COVID-19. A Comparative Review of SARS-CoV-2 Coronavirus Laboratory and Point-of-Care Diagnostics

Kubina, Robert; Dziedzic, Arkadiusz
Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. This would facilitate an appropriate treatment, a prompt isolation and consequently deceleration of the pandemic. Various laboratory tests can identify the genetic material of SARS-CoV-2 that causes COVID-19 in specimens, or specific anti-viral antibodies in blood/serum. Due to the current pandemic situation, a development of point-of-care diagnostics (POCD) allows us to substantially accelerate taking clinical decisions and implement strategic planning at the national level of preventative measures. This review summarizes and compares the available POCD and those currently under development, including quantitative reverse transcription PCR (RT-qPCR), serology immunoassays (SIAs) and protein microarray method (PMM) designed for standard and rapid COVID-19 diagnosis.

On‐Chip Neo‐Glycopeptide Synthesis for Multivalent Glycan Presentation

Mende, Marco; Tsouka, Alexandra; Heidepriem, Jasmin; Paris, Grigori; Mattes, Daniela S.; Eickelmann, Stephan; Bordoni, Vittorio; Wawrzinek, Robert; Fuchsberger, Felix F.; Seeberger, Peter H.; Rademacher, Christoph; Delbianco, Martina; Mallagaray, Alvaro; Loeffler, Felix F
Chem. Eur. J..
Apr 2020
Single glycan–protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent display. Laser-based array synthesis technology allows for flexible and rapid on-surface synthesis of different peptides. By combining this technique with click chemistry, neo-glycopeptides were produced directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well-defined glycan structures for multivalent display. The two lectins concanavalin A and langerin were probed with different glycans on multivalent scaffolds, revealing strong spacing-, density-, and ligand-dependent binding. In addition, we could also measure the surface dissociation constant. This approach allows for a rapid generation, screening, and optimization of a multitude of multivalent scaffolds for glycan binding.

Autoantibody Signature in Cardiac Arrest

Maguy, Ange; Tardif, Jean-Claude; Busseuil, David; Ribi, Camillo; Li, Jin
Circulation.
Apr 2020
Background: Cardiac arrest is a tragic event that causes one death roughly every 90 seconds worldwide. Survivors generally undergo a work-up to identify the etiology of arrest. However, 5-10% of cardiac arrest remain unexplained. As cardiac arrhythmias mostly underlie cardiac arrest and increasing evidence strongly supports the involvement of autoantibodies in arrhythmogenesis, a large-panel autoantibody screening was performed in cardiac arrest patients. Methods: This is an observational, cross-sectional study of patients from the Montreal Heart Institute (MHI) hospital cohort, a single center registry of participants. A peptide microarray was designed to screen for IgG targeting epitopes from all known cardiac ion channels with extracellular domains. Plasma samples from 23 patients with unexplained cardiac arrest were compared to 22 cardiac arrest cases of ischemic origin and a group of 29 age-, sex- and BMI-matched healthy subjects. The false discovery rate (FDR), LASSO logistic regression and random forest methods were jointly carried out to find significant differential IgG responses. Results: The autoantibody against the pore domain of the L-type voltage-gated calcium channel (Ca v 1.2) was consistently identified as a biomarker of idiopathic cardiac arrest (P=0.002, FDR=0.007, classification accuracies ≥0.83). Functional studies on human induced pluripotent stem cell-derived cardiomyocytes demonstrated that the anti-Ca v 1.2 IgG purified from patients with idiopathic cardiac arrest is proarrhythmogenic by reducing the action potential duration through calcium channel inhibition. Conclusions: The present report addresses the concept of autoimmunity and cardiac arrest. Hitherto unknown autoantibodies targeting extracellular sequences of cardiac ion channels were detected. Moreover, the study identified an autoantibody signature specific to patients with cardiac arrest.

Plasmodium Falciparum and Plasmodium Vivax Vaccine

Werner, Ekkehard
Apr 2020
The present invention relates to a vaccine V comprising (A) at least one isolated polypeptide strand P comprising or consisting of at least nine consecutive amino acid moieties of the repetitive organellar protein, putative of Plasmodium falciparum or the hypothetical protein PVNG_04523 of Plasmodium vivax or a polynucleotide strand encoding for such polypeptide; and (B) at least one pharmaceutically acceptable carrier or excipient. Furthermore, the present invention refers to an antibody binding to the repetitive organellar protein,putative of Plasmodium falciparumor the hypothetical protein PVNG_04523 of Plasmodium vivax or a polynucleotide strand encoding therefor, to a method of generating such antibody and uses thereof.

Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

Dreyfus, David H.; Farina, Antonella; Farina, Giuseppina Alessandra
Immunol Res.
Dec 2018
EBV (Epstein-Barr Virus) and other human DNA viruses are associated with autoimmune syndromes in epidemiologic studies. In this work, immunoglobulin G response to EBV-encoded proteins which share regions with human immune response proteins from the human host including ZEBRA (BZLF-1 encoded protein), BALF-2 recombinase expressed primarily during the viral lytic replication cycle, and EBNA-1 (Epstein-Barr Virus Nuclear Antigen) expressed during the viral latency cycle respectively were characterized using a laser-printed micro-array (PEPperprint.com). IgG response to conserved “A/T hooks” in EBV-encoded proteins such as EBNA-1 and the BALF-2 recombinase related to host DNA-binding proteins including RAG-1 recombinase and histones, and EBV-encoded virokines such as the IL-10 homologue BCRF-1 suggest further directions for clinical research. The author suggests that proteomic “molecular fingerprints” of the immune response to viral proteins shared with human immune response genes are potentially useful in early diagnosis and monitoring of autoantibody production and response to therapy in EBV-related autoimmune syndromes.

Soybean Allergy Related Epitopes

Kern, Karolin; Spiegel, Holger; Havenith, Heide; Szardenings, Michael
Nov 2018
The invention relates to a compilation comprising at least five different peptides, each peptide comprising at least one sequence element corresponding to an epitope selected from the group consisting of SEQ ID NO.: 1-354, wherein at least five different epitopes are represented. The invention further relates to an in vitro method for determining a patient’s immune status to soybean allergens, to a method for detecting at least one soybean allergen in a substance and to a method for determining the allergenicity of a soybean variety. Additionally, the invention relates to a kit comprising at least one composition containing a compound comprising at least five different sequence elements each corresponding to an epitope selected from the group consisting of SEQ ID NO.: 1-354, wherein at least five different epitopes are represented. Furthermore, the invention relates to the use of a peptide comprising a sequence element corresponding to an epitope for providing a molecule binding to a protein or peptide comprising the epitope.

Linear epitopes in Onchocerca volvulus vaccine candidate proteins and excretory-secretory proteins

Lagatie, Ole; Verheyen, Ann; Van Dorst, Bieke; Batsa Debrah, Linda; Debrah, Alex; Stuyver, Lieven J.
Parasite Immunol.
Nov 2018
In our previous study, a proteome-wide screen was conducted to identify linear epitopes in this parasite’s proteome, resulting in the discovery of three immunodominant motifs. Here, we investigated whether such antigenic peptides were found in proteins that were already known as vaccine candidates and excretome/secretome proteins for Onchocerca volvulus This approach led to the identification of 71 immunoreactive stretches in 46 proteins. A deep-dive into the immunoreactivity profiles of eight vaccine candidates that were chosen as most promising candidates for further development (Ov-CPI-2, Ov-ALT-1, Ov-RAL-2, Ov-ASP-1, Ov-103, Ov-RBP-1, Ov-CHI-1, and Ov-B20), resulted in the identification of a poly-glutamine stretch in Ov-RAL-2 that has properties for use as a serodiagnostic marker for O. volvulus infection. A peptide ELISA was developed, and the performance of this assay was evaluated. Based on this assessment, it was found that this assay has a sensitivity of 75.0% [95% CI: 64.9%-83.5%] and a specificity of 98.5% [95% CI: 94.6%-99.8%]. Furthermore, 8.7% reactivity in Asian parasite-infected individuals (8 out of 92) was observed. Besides this identification of a linear epitope marker, the information on the presence of linear epitopes in vaccine candidate proteins might be useful in the study of vaccines for river blindness.

Quote form