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

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Scoping review of the applications of peptide microarrays on the fight against human infections

Vengesai, Arthur; Kasambala, Maritha; Mutandadzi, Hamlet; Mduluza-Jokonya, Tariro L.; Mduluza, Takafira; Naicker, Thajasvarie
PLoS ONE.
Jan 2022
10.1371/journal.pone.0248666
Introduction This scoping review explores the use of peptide microarrays in the fight against infectious diseases. The research domains explored included the use of peptide microarrays in the mapping of linear B-cell and T cell epitopes, antimicrobial peptide discovery, immunosignature characterisation and disease immunodiagnostics. This review also provides a short overview of peptide microarray synthesis. Methods Electronic databases were systematically searched to identify relevant studies. The review was conducted using the Joanna Briggs Institute methodology for scoping reviews and data charting was performed using a predefined form. The results were reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Results Ninety-five articles from 103 studies were included in the final data charting process. The majority (92. 0%) of the articles were published during 2010–2020 and were mostly from Europe (44.2%) and North America (34.7%). The findings were from the investigation of viral (45.6%), bacterial (32. 0%), parasitic (23.3%) and fungal (2. 0%) infections. Out of the serological studies, IgG was the most reported antibody type followed by IgM. The largest portion of the studies (77.7%) were related to mapping B-cell linear epitopes, 5.8% were on diagnostics, 5.8% reported on immunosignature characterisation and 8.7% reported on viral and bacterial cell binding assays. Two studies reported on T-cell epitope profiling. Conclusion The most important application of peptide microarrays was found to be B-cell epitope mapping or antibody profiling to identify diagnostic and vaccine targets. Immunosignatures identified by random peptide microarrays were found to be applied in the diagnosis of infections and interrogation of vaccine responses. The analysis of the interactions of random peptide microarrays with bacterial and viral cells using binding assays enabled the identification of antimicrobial peptides. Peptide microarray arrays were also used for T-cell linear epitope mapping which may provide more information for the design of peptide-based vaccines and for the development of diagnostic reagents.

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

Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus

Kleer, Jessica S.; Rabatscher, Pascal A.; Weiss, Jessica; Leonardi, Joel; Vogt, Severin B.; Kieninger-Gräfitsch, Andrea; Chizzolini, Carlo; Huynh-Do, Uyen; Ribi, Camillo; Trendelenburg, Marten
Front. Immunol..
Jan 2022
10.3389/fimmu.2021.761395
Objective In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. Methods First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. Results The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. Conclusion In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.

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.

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.

Mus81-Mms4 endonuclease is an Esc2-STUbL-Cullin8 mitotic substrate impacting on genome integrity

Waizenegger, Anja; Urulangodi, Madhusoodanan; Lehmann, Carl P.; Reyes, Teresa Anne Clarisse; Saugar, Irene; Tercero, José Antonio; Szakal, Barnabas; Branzei, Dana
Nov 2020
10.1038/s41467-020-19503-4
The Mus81-Mms4 nuclease is activated in G2/M via Mms4 phosphorylation to allow resolution of persistent recombination structures. However, the fate of the activated phosphorylated Mms4 remains unknown. Here we find that Mms4 is engaged by (poly)SUMOylation and ubiquitylation and targeted for proteasome degradation, a process linked to the previously described Mms4 phosphorylation cycle. Mms4 is a mitotic substrate for the SUMO-Targeted Ubiquitin ligase Slx5/8, the SUMO-like domain-containing protein Esc2, and the Mms1-Cul8 ubiquitin ligase. In the absence of these activities, phosphorylated Mms4 accumulates on chromatin in an active state in the next G1, subsequently causing abnormal processing of replication-associated recombination intermediates and delaying the activation of the DNA damage checkpoint. Mus81-Mms4 mutants that stabilize phosphorylated Mms4 have similar detrimental effects on genome integrity. Overall, our findings highlight a replication protection function for Esc2-STUbL-Cul8 and emphasize the importance for genome stability of resetting phosphorylated Mms4 from one cycle to another.

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.

SARS-CoV-2 epitope mapping on microarrays highlights strong immune-response to N protein region

Musicò, Angelo; Frigerio, Roberto; Mussida, Alessandro; Barzon, Luisa; Sinigaglia, Alessandro; Riccetti, Silvia; Gobbi, Federico; Piubelli, Chiara; Bergamaschi, Greta; Chiari, Marcella; Gori, Alessandro; Cretich, Marina
Nov 2020
10.1101/2020.11.09.374082

Abstract

A workflow for SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 Spike (S), Nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155-171) providing 92% sensitivity and 100% specificity of IgG detection in Covid-19 samples thus being a promising candidate for rapid implementation in serological tests.

Generation of Chicken IgY against SARS-COV-2 Spike Protein and Epitope Mapping

Lu, Yan; Wang, Yajun; Zhang, Zhen; Huang, Jingliang; Yao, Meicun; Huang, Guobin; Ge, Yuanyuan; Zhang, Peichun; Huang, Huaxin; Wang, Yong; Li, Huiliang; Wang, Wen
Oct 2020
This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.

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.

Novel Anti-Cd40 Antibodies and Use Thereof

Park, Chung Gyu; Kim, Jung Sik; Lucas, Zachariah
Sep 2020
The present invention relates to novel anti-CD40 antibodies and a use thereof and, more specifically, provided are a pharmaceutical composition for treating or preventing autoimmune diseases and a composition for inhibiting immune rejection during organ transplantation, both compositions containing, as an active ingredient, novel anti-CD40 antibodies that specifically bind to a novel epitope of CD40. Novel anti-CD40 antibodies of the present invention directly target CD40, but not CD40 ligands, and block the signaling of CD40-CD154 without stimulating platelets so as to exhibit excellent antagonistic effects, thereby being expected to be usable as a preparation effective in the treatment of autoimmune diseases and the inhibition of organ transplantation rejection.

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