Enhancing Antibody Serodiagnosis Using a Controlled Peptide Coimmobilization Strategy

ACS Infect Dis. 2018 Jun 8;4(6):998-1006. doi: 10.1021/acsinfecdis.8b00014. Epub 2018 Mar 29.

Abstract

Antigen immunoreactivity is often determined by surface regions defined by the 3D juxtapositions of amino acids stretches that are not continuous in the linear sequence. As such, mimicking an antigen immunoreactivity by means of putative linear peptide epitopes for diagnostic purposes is not trivial. Here we present a straightforward and robust method to extend the reach of immune-diagnostic probes design by copresenting peptides belonging to the same antigenic surface. In this case study focused on a computationally predicted Zika virus NS1 protein putative antigenic region, we reached a diagnostic confidence by the oriented and spatially controlled coimmobilization of peptide sequences found adjacent within the protein fold, that cooperatively interacted to provide enhanced immunoreactivity with respect to single linear epitopes. Through our method, we were able to differentiate Zika infected individuals from healthy controls. Remarkably, our strategy fits well with the requirements to build high-throughput screening platforms of linear and mixed peptide libraries, and it could possibly facilitate the rapid identification of conformational immunoreactive regions.

Keywords: Zika virus; arbovirus; clickable polymer; discontinuous epitopes; microarrays; peptide bioprobes; peptide design; serodiagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies / immunology*
  • Epitope Mapping / methods
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Humans
  • Models, Molecular
  • Molecular Probes
  • Peptides / chemistry
  • Peptides / immunology*
  • Protein Conformation
  • ROC Curve
  • Reproducibility of Results
  • Serologic Tests / methods*
  • Serologic Tests / standards
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / immunology
  • Zika Virus / immunology
  • Zika Virus Infection / diagnosis
  • Zika Virus Infection / immunology
  • Zika Virus Infection / virology

Substances

  • Antibodies
  • Epitopes
  • Molecular Probes
  • NS1 protein, zika virus
  • Peptides
  • Viral Nonstructural Proteins