Contact
Quote

Home » Publications » Page 2

Publications

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

Filter by
Filtered (24)
Filters
Show (24)
Cancel
Showing most recent

Development and Optimization of Bifunctional Fusion Proteins to Locally Modulate Complement Activation in Diseased Tissue

Fahnoe, Kelly C.; Liu, Fei; Morgan, Jennifer G.; Ryan, Sarah T.; Storek, Michael; Stark, Ellen Garber; Taylor, Fred R.; Holers, V. Michael; Thurman, Joshua M.; Wawersik, Stefan; Kalled, Susan L.; Violette, Shelia M.
Front Immunol.
Jun 2022
10.3389/fimmu.2022.869725
Sustained complement activation is an underlying pathologic driver in many inflammatory and autoimmune diseases. Currently approved anti-complement therapies are directed at the systemic blockade of complement. Consequently, these therapies provide widespread inhibition of complement pathway activity, beyond the site of ongoing activation and the intended pharmacodynamic (PD) effects. Given the essential role for complement in both innate and adaptive immunity, there is a need for therapies that inhibit complement in diseased tissue while limiting systemic blockade. One potential approach focuses on the development of novel fusion proteins that enable tissue-targeted delivery of complement negative regulatory proteins. These therapies are expected to provide increased potency and prolonged tissue PD, decreased dosing frequency, and the potential for improved safety profiles. We created a library of bifunctional fusion proteins that direct a fragment of the complement negative regulator, complement receptor type 1 (CR1) to sites of tissue injury. Tissue targeting is accomplished through the binding of the fusion protein to complement C3 fragments that contain a surface-exposed C3d domain and which are covalently deposited on tissues where complement is being activated. To that end, we generated a fusion protein that contains an anti-C3d monoclonal antibody recombinantly linked to the first 10 consensus repeats of CR1 (CR11-10) with the intention of delivering high local concentrations of this complement negative regulatory domain to tissue-bound complement C3 fragments iC3b, C3dg and C3d. Biochemical and in vitro characterization identified several fusion proteins that inhibit complement while maintaining the C3d domain binding properties of the parent monoclonal antibody. Preclinical in vivo studies further demonstrate that anti-C3d fusion proteins effectively distribute to injured tissue and reduce C3 fragment deposition for periods beyond 14 days. The in vitro and in vivo profiles support the further evaluation of C3d mAb-CR11-10 as a novel approach to restore proper complement activation in diseased tissue in the absence of continuous systemic complement blockade.

Anti-COX-2 Autoantibody is a Novel Marker of Immune Aplastic Anemia

Kelkka, Tiina; Tyster, Mikko; Lundgren, Sofie; Feng, Xingmin; Kerr, Cassandra; Hosokawa, Kohei; Huuhtanen, Jani; Keränen, Mikko; Kawakami, Toru; Patel, Bhavisha; Maeda, Yuka; Nieminen, Otso; Kasanen, Tiina; Aronen, Pasi; Yadav, Bhagwan; Rajala, Hanna; Nakazawa, Hideyuki; Jaatinen, Taina; Hellstrom-Lindberg, Eva; Ogawa, Seishi; Ishida, Fumihiro; Nishikawa, Hiroyoshi; Nakao, Shinji; Maciejewski, Jaroslaw; Young, Neal S.; Mustjoki, Satu
May 2022
10.21203/rs.3.rs-1653776/v1
In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing > 9 000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclo-oxygenase 2 (COX-2, aCOX-2 Ab). 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the > 40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable diagnostic tool.

γδ T cells license immature B cells to produce a broad range of polyreactive antibodies

Rampoldi, Francesca; Donato, Elisa; Ullrich, Leon; Deseke, Malte; Janssen, Anika; Demera, Abdi; Sandrock, Inga; Bubke, Anja; Juergens, Anna-Lena; Swallow, Maxine; Sparwasser, Tim; Falk, Christine; Tan, Likai; Trumpp, Andreas; Prinz, Immo
Cell Reports.
May 2022
10.1016/j.celrep.2022.110854
Immature autoreactive B cells are present in all healthy individuals, but it is unclear which signals are required for their maturation into antibody-producing cells. Inducible depletion of γδ T cells show that direct interaction between γδ T cells and immature B cells in the spleen support an “innate” transition to mature B cells with a broad range of antigen specificities. IL-4 production of γδ T cells and cell-to-cell contact via CD30L support B cell maturation and induce genes of the unfolded protein response and mTORC1 signaling. Eight days after in vivo depletion of γδ T cells, increased numbers of B cells are already stuck in the transitional phase and express increased levels of IgD and CD21. Absence of γδ T cells leads also to reduced levels of serum anti-nuclear autoantibodies, making γδ T cells an attractive target to treat autoimmunity.

Clonal expansion and markers of directed mutation of IGHV4-34 B cells in plasmablasts during Kawasaki disease

Chang, Arthur J.; Baron, Sarah; Hoffman, Jonathon; Hicar, Mark D.
Molecular Immunology.
May 2022
10.1016/j.molimm.2022.03.011
Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The cause remains unknown; however, epidemiologic and demographic data support a single preceding infectious agent may lead to KD. A variety of pathophysiologic responses have been proposed, including direct invasion of the coronary arteries, a superantigen response, and a post-infectious autoimmune phenomenon. A role for B cell responses during KD are supported by numerous findings including B cell specific markers identified in genome wide association studies. We have recently published data showing children with KD have similar plasmablast (PB) responses to children with infections. Since during other infections, cells expressing antibodies against the preceding infection are enriched in PBs, we sought to explore the specific antibodies encoded by PBs during KD. In one child we see a massive expansion in IGHV4–34 utilizing antibodies, which has been associated with autoimmunity in the past. We further explored this expansion of IGHV4–34 utilization during the peripheral PB rise with next generation sequencing (NGS) analysis and utilizing newer techniques of chromium chip single cell separation (10x Genomics®). We also utilized peptide array screening to attempt to identify an antigen to the most prolific clones.

Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH

Parsons, Andrea J.; Ophir, Sabrina I.; Duty, J. Andrew; Kraus, Thomas A.; Stein, Kathryn R.; Moran, Thomas M.; Tortorella, Domenico
Commun Biol.
Apr 2022
10.1038/s42003-022-03294-z
Human cytomegalovirus (HCMV) is a β-herpesvirus that increases morbidity and mortality in immunocompromised individuals including transplant recipients and newborns. New anti-HCMV therapies are an urgent medical need for diverse patient populations. HCMV infection of a broad range of host tissues is dependent on the gH/gL/gO trimer and gH/gL/UL28/UL130/UL131A pentamer complexes on the viral envelope. We sought to develop safe and effective therapeutics against HCMV by generating broadly-neutralizing, human monoclonal antibodies (mAbs) from VelocImmune® mice immunized with gH/gL cDNA. Following high-throughput binding and neutralization screening assays, 11 neutralizing antibodies were identified with unique CDR3 regions and a high-affinity (KD 1.4-65 nM) to the pentamer complex. The antibodies bound to distinct regions within Domains 1 and 2 of gH and effectively neutralized diverse clinical strains in physiologically relevant cell types including epithelial cells, trophoblasts, and monocytes. Importantly, combined adminstration of mAbs with ganciclovir, an FDA approved antiviral, greatly limited virus dissemination. Our work identifies several anti-gH/gL mAbs and sheds light on gH neutralizing epitopes that can guide future vaccine strategies.

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.

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.

Single-Molecule Detection on a Protein-Array Assay Platform for the Exposure of a Tuberculosis Antigen

Schmidt, Ronny; Jacak, Jaroslaw; Schirwitz, Christopher; Stadler, Volker; Michel, Gerd; Marmé, Nicole; Schütz, Gerhard J.; Hoheisel, Jörg D.; Knemeyer, Jens-Peter
J. Proteome Res..
Jan 2011
10.1021/pr101070j

Quote form