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Molecular & Cellular Proteomics

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Research

High-density peptide arrays help to identify linear immunogenic B cell epitopes in individuals naturally exposed to malaria infection

Thomas Jaenisch, Kirsten Heiss, Nico Fischer, Carolin Geiger, F Ralf Bischoff, Gerhard Moldenhauer, Leszek Rychlewski, Ali Sié, Boubacar Coulibaly, Peter H. Seeberger, Lucjan S Wyrwicz, Frank Breitling and Felix F Loeffler  Correspondence email
Molecular & Cellular Proteomics January 10, 2019, mcp.RA118.000992; https://doi.org/10.1074/mcp.RA118.000992
Thomas Jaenisch
Center for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany, Germany
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Kirsten Heiss
Center for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany, Germany
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Nico Fischer
Center for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany, Germany
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Carolin Geiger
Center for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany, Germany
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F Ralf Bischoff
German Cancer Research Center, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany, Germany
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Gerhard Moldenhauer
German Cancer Research Center, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany, Germany
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Leszek Rychlewski
BioInfoBank Institute, Św. Marcin 80/82 lok. 355, 61-809 Poznań, Poland, Poland
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Ali Sié
Centre de Recherche en Santé de Nouna, BP 02 Nouna, Rue Namory Keita, Burkina Faso, Burkina Faso
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Boubacar Coulibaly
Centre de Recherche en Santé de Nouna, BP 02 Nouna, Rue Namory Keita, Burkina Faso, Burkina Faso
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Peter H. Seeberger
Max Planck Institute of Colloids and Interfaces
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Lucjan S Wyrwicz
Department of Oncology and Radiotherapy, M Sklodowska Curie Memorial Cancer Center, Wawelska 15, 02-034 Warsaw, Poland, Poland
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Frank Breitling
Institute of Microstructure Technology, Karlsruhe Institute of Technology, Germany, Hermann-von-Helmholtz-Platz 1, D 76344 Eggenstein-Leopoldshafen, Germany, Germany
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Felix F Loeffler
Max-Planck-Institute of Colloids and Interfaces, Germany
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  • For correspondence: felix.loeffler@mpikg.mpg.de
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Abstract

High-density peptide arrays are an excellent means to profile anti-plasmodial antibody responses. Different protein intrinsic epitopes can be distinguished and additional insights are gained, when compared to assays involving the full-length protein. Distinct reactivities to specific epitopes within one protein may explain differences in published results, regarding immunity or susceptibility to malaria. We pursued three approaches to find specific epitopes within important plasmodial proteins, (1) twelve leading vaccine candidates were mapped as overlapping 15-mer peptides, (2) a bioinformatical approach served to predict immunogenic malaria epitopes which were subsequently validated in the assay, and (3) randomly selected peptides from the malaria proteome were screened as a control. Several peptide array replicas were prepared, employing particle-based laser printing, and were used to screen 27 serum samples from a malaria-endemic area in Burkina Faso, West Africa. The immunological status of the individuals was classified as ‘protected’ or ‘unprotected’ based on clinical symptoms, parasite density, and age. The vaccine candidate screening approach resulted in significant hits in all twelve proteins and allowed us (i) to verify many known immunogenic structures, (ii) to map B cell epitopes across the entire sequence of each antigen and (iii) to uncover novel immunogenic epitopes. Predicting immunogenic regions in the proteome of the human malaria parasite Plasmodium falciparum, via the bioinformatics approach and subsequent array screening, confirmed known immunogenic sequences, such as in the leading malaria vaccine candidate CSP and discovered immunogenic epitopes derived from hypothetical or unknown proteins

  • epitope mapping
  • Antibodies*
  • Biomarker: Diagnostic
  • Malaria
  • Peptide array
  • Peptidomics

Footnotes

  • Author contributions: T.J., K.H., C.G., G.M., L.R., A.S., B.C., P.H.S., L.S.W., F.B., and F.F.L. designed research; T.J., K.H., N.F., C.G., F.R.B., L.R., L.S.W., and F.F.L. performed research; T.J., K.H., P.H.S., and F.F.L. wrote the paper; K.H., N.F., L.R., L.S.W., and F.F.L. analyzed data; F.R.B., G.M., L.R., A.S., B.C., and F.F.L. contributed new reagents/analytic tools.

  • Received July 27, 2018.
  • Revision received November 28, 2018.
  • Accepted January 10, 2019.
  • Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
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High-density peptide arrays help to identify linear immunogenic B cell epitopes in individuals naturally exposed to malaria infection
Thomas Jaenisch, Kirsten Heiss, Nico Fischer, Carolin Geiger, F Ralf Bischoff, Gerhard Moldenhauer, Leszek Rychlewski, Ali Sié, Boubacar Coulibaly, Peter H. Seeberger, Lucjan S Wyrwicz, Frank Breitling, Felix F Loeffler
Molecular & Cellular Proteomics January 10, 2019, mcp.RA118.000992; DOI: 10.1074/mcp.RA118.000992

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High-density peptide arrays help to identify linear immunogenic B cell epitopes in individuals naturally exposed to malaria infection
Thomas Jaenisch, Kirsten Heiss, Nico Fischer, Carolin Geiger, F Ralf Bischoff, Gerhard Moldenhauer, Leszek Rychlewski, Ali Sié, Boubacar Coulibaly, Peter H. Seeberger, Lucjan S Wyrwicz, Frank Breitling, Felix F Loeffler
Molecular & Cellular Proteomics January 10, 2019, mcp.RA118.000992; DOI: 10.1074/mcp.RA118.000992
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