Computational and Experimental Validation of B and T-cell Epitopes of the in Vivo Immune Response to a Novel Malarial Antigen

PLoS One. 2013 Aug 16;8(8):e71610. doi: 10.1371/journal.pone.0071610. eCollection 2013.

Abstract

Vaccine development efforts will be guided by algorithms that predict immunogenic epitopes. Such prediction methods rely on classification-based algorithms that are trained against curated data sets of known B and T cell epitopes. It is unclear whether this empirical approach can be applied prospectively to predict epitopes associated with protective immunity for novel antigens. We present a comprehensive comparison of in silico B and T cell epitope predictions with in vivo validation using an previously uncharacterized malaria antigen, CelTOS. CelTOS has no known conserved structural elements with any known proteins, and thus is not represented in any epitope databases used to train prediction algorithms. This analysis represents a blind assessment of this approach in the context of a novel, immunologically relevant antigen. The limited accuracy of the tested algorithms to predict the in vivo immune responses emphasizes the need to improve their predictive capabilities for use as tools in vaccine design.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology*
  • Cathepsins / metabolism
  • Cell Line
  • Computational Biology / methods*
  • Computer Simulation
  • Epitope Mapping
  • Epitopes, B-Lymphocyte / chemistry*
  • Epitopes, B-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / chemistry*
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Humans
  • Immunity / immunology*
  • Immunity, Cellular / immunology
  • Malaria / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Plasmodium falciparum / immunology
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Conformation
  • Rabbits
  • Reproducibility of Results

Substances

  • Antigens, Protozoan
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Cathepsins
  • Proteasome Endopeptidase Complex

Grant support

This work was supported by the U.S. Agency for International Development under project number 936–3118, award number GHA-T-00-08-00007-01, and by the United States Army Medical Research and Materiel Command. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.