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

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Rise of the SARS-CoV-2 Variants: can proteomics be the silver bullet?

Acharjee, Arup; Stephen Kingsly, Joshua; Kamat, Madhura; Kurlawala, Vishakha; Chakraborty, Aparajita; Vyas, Priyanka; Vaishnav, Radhika; Srivastava, Sanjeeva
Expert Rev Proteomics.
Jun 2022
10.1080/14789450.2022.2085564
INTRODUCTION: The challenges posed by emergent strains of SARS-CoV-2 need to be tackled by contemporary scientific approaches, with proteomics playing a significant role. AREAS COVERED: In this review, we provide a brief synthesis of the impact of proteomics technologies in elucidating disease pathogenesis and classifiers for the prognosis of COVID-19 and propose proteomics methodologies that could play a crucial role in understanding emerging variants and their altered disease pathology. From aiding the design of novel drug candidates to facilitating the identification of T cell vaccine targets, we have discussed the impact of proteomics methods in COVID-19 research. Techniques varied as mass spectrometry, single-cell proteomics, multiplexed ELISA arrays, high-density proteome arrays, surface plasmon resonance, immunopeptidomics, and in silico docking studies that have helped augment the fight against existing diseases were useful in preparing us to tackle SARS-CoV-2 variants. We also propose an action plan for a pipeline to combat emerging pandemics using proteomics technology by adopting uniform standard operating procedures and unified data analysis paradigms. EXPERT OPINION: The knowledge about the use of diverse proteomics approaches for COVID-19 investigation will provide a framework for future basic research, better infectious disease prevention strategies, improved diagnostics, and targeted therapeutics.

Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis

D’Alessandro-Gabazza, Corina N.; Yasuma, Taro; Kobayashi, Tetsu; Toda, Masaaki; Abdel-Hamid, Ahmed M.; Fujimoto, Hajime; Hataji, Osamu; Nakahara, Hiroki; Takeshita, Atsuro; Nishihama, Kota; Okano, Tomohito; Saiki, Haruko; Okano, Yuko; Tomaru, Atsushi; Fridman D’Alessandro, Valeria; Shiraishi, Miyako; Mizoguchi, Akira; Ono, Ryoichi; Ohtsuka, Junpei; Fukumura, Masayuki; Nosaka, Tetsuya; Mi, Xuenan; Shukla, Diwakar; Kataoka, Kensuke; Kondoh, Yasuhiro; Hirose, Masaki; Arai, Toru; Inoue, Yoshikazu; Yano, Yutaka; Mackie, Roderick I.; Cann, Isaac; Gabazza, Esteban C.
Nat Commun.
Mar 2022
10.1038/s41467-022-29064-3
Idiopathic pulmonary fibrosis is an incurable disease of unknown etiology. Acute exacerbation of idiopathic pulmonary fibrosis is associated with high mortality. Excessive apoptosis of lung epithelial cells occurs in pulmonary fibrosis acute exacerbation. We recently identified corisin, a proapoptotic peptide that triggers acute exacerbation of pulmonary fibrosis. Here, we provide insights into the mechanism underlying the processing and release of corisin. Furthermore, we demonstrate that an anticorisin monoclonal antibody ameliorates lung fibrosis by significantly inhibiting acute exacerbation in the human transforming growth factorβ1 model and acute lung injury in the bleomycin model. By investigating the impact of the anticorisin monoclonal antibody in a general model of acute lung injury, we further unravel the potential of corisin to impact such diseases. These results underscore the role of corisin in the pathogenesis of acute exacerbation of pulmonary fibrosis and acute lung injury and provide a novel approach to treating this incurable disease.

Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome

Fathi, Anahita; Dahlke, Christine; Krähling, Verena; Kupke, Alexandra; Okba, Nisreen M. A.; Raadsen, Matthijs P.; Heidepriem, Jasmin; Müller, Marcel A.; Paris, Grigori; Lassen, Susan; Klüver, Michael; Volz, Asisa; Koch, Till; Ly, My L.; Friedrich, Monika; Fux, Robert; Tscherne, Alina; Kalodimou, Georgia; Schmiedel, Stefan; Corman, Victor M.; Hesterkamp, Thomas; Drosten, Christian; Loeffler, Felix F.; Haagmans, Bart L.; Sutter, Gerd; Becker, Stephan; Addo, Marylyn M.
Feb 2022
10.1101/2022.02.14.22270168
Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials.

Analysis of the Immune Response and Identification of Antibody Epitopes Against the Sigma C Protein of Avian Orthoreovirus Following Immunization with Live or Inactivated Vaccines

Dawe, W. H.; Kapczynski, D. R.; Linnemann, E. G.; Gauthiersloan, V. R.; Sellers, H. S.
Avian Diseases.
Jan 2022
10.1637/aviandiseases-D-22-99992

A Quantum Vaccinomics Approach Based on Protein–Protein Interactions

Contreras, Marinela; Artigas-Jerónimo, Sara; Pastor Comín, Juan J.; de la Fuente, José
Jan 2022
10.1007/978-1-0716-1888-2_17
Vaccines are the most effective preventive intervention to reduce the impact of infectious diseases worldwide. In particular, tick-borne diseases represent a growing burden for human and animal health worldwide and vaccines are the most effective and environmentally sound approach for the control of vector infestations and pathogen transmission. However, the development of effective vaccines for the control of tick-borne diseases with combined vector-derived and pathogen-derived antigens is one of the limitations for the development of effective vaccine formulations. Quantum biology arise from findings suggesting that living cells operate under non-trivial features of quantum mechanics, which has been proposed to be involved in DNA mutation biological process. Then, the electronic structure of the molecular interactions behind peptide immunogenicity led to quantum immunology and based on the definition of the photon as a quantum of light, the immune protective epitopes were proposed as the immunological quantum. Recently, a quantum vaccinomics approach was proposed based on the characterization of the immunological quantum to further advance the design of more effective and safe vaccines. In this chapter, we describe methods of the quantum vaccinomics approach based on proteins with key functions in cell interactome and regulome of vector–host–pathogen interactions for the identification by yeast two-hybrid screen and the characterization by in vitro protein–protein interactions and musical scores of protein interacting domains, and the characterization of conserved protective epitopes in protein interacting domains. These results can then be used for the design and production of chimeric protective antigens.

Protein microarrays for COVID-19 research: Biomarker discovery, humoral response, and vaccine targets

Acharjee, Arup; Barpanda, Abhilash; Ren, Jing; Yu, Xiaobo
Jan 2022
10.1201/9781003220787-6
Of all the technological interventions used to probe the COVID-19 biological sample, microarrays have provided unique information about the biology of SARS-CoV-2 infection in the greatest of detail. Protein microarrays are available in various formats such as protein microarray, antibody microarray, and peptide microarrays. These provide an attractive format to study host response against infection, with its straightforward sample preparation strategy and easy result analysis pipelines. Microarray technology either uses antibodies against hundreds of proteins to study host proteins or scans immunogenic peptides of the pathogen in a microarray panel of the pathogen proteome. It can be used to study the humoral immune response against antigenic proteins of the SARS-CoV-2 virus, host proteomic alterations due to the infection. The SARS-CoV-2 peptide array can be used for the accurate detection of antigenic determinants for vaccine design. This chapter summarizes the different types of protein and peptide microarray and their use in COVID-19 biomarker discovery, disease management, vaccine design, etc., for better management of COVID-19.

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
Sep 2020
10.1111/cea.13730
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
10.1021/acs.jproteome.0c00484
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.

Expression of different L1 isoforms of Mastomys natalensis papillomavirus as mechanism to circumvent adaptive immunity

Fu, Yingying; Cao, Rui; Schäfer, Miriam; Stephan, Sonja; Braspenning-Wesch, Ilona; Schmitt, Laura; Bischoff, Ralf; Müller, Martin; Schäfer, Kai; Vinzón, Sabrina E; Rösl, Frank; Hasche, Daniel
Aug 2020
10.7554/eLife.57626
Although many high-risk mucosal and cutaneous human papillomaviruses (HPVs) theoretically have the potential to synthesize L1 isoforms differing in length, previous seroepidemiological studies only focused on the short L1 variants, co-assembling with L2 to infectious virions. Using the multimammate mouse Mastomys coucha as preclinical model, this is the first study demonstrating seroconversion against different L1 isoforms during the natural course of papillomavirus infection. Intriguingly, positivity with the cutaneous MnPV was accompanied by a strong seroresponse against a longer L1 isoform, but to our surprise, the raised antibodies were non-neutralizing. Only after a delay of around 4 months, protecting antibodies against the short L1 appeared, enabling the virus to successfully establish an infection. This argues for a novel humoral immune escape mechanism that may also have important implications on the interpretation of epidemiological data in terms of seropositivity and protection of PV infections in general.

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