The molecular basis of virus crossreactivity and neutralisation after immunisation with optimised chimeric peptides mimicking a putative helical epitope of the measles virus hemagglutinin protein

Karim C.El Kasmi, Dietmar Theisen, Nicolaas H.C. Brons, Claude P. Muller*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

The loop comprising aminoacids H236-256, connects two strands of sheet 1 of the propeller-like hemagglutinin (H) protein of the measles virus (MV) and contains a putative active site residue (R253), a residue implicated in CD46-downregulation (R243) and the minimal epitope E245L-QL249 of the neutralising and protective monoclonal antibody BH129. The objective of this study was to design synthetic peptides which induce neutralising antibodies against this important functional domain. Peptide-design was based on the colinear synthesis of this sequential B cell epitope (BCE) with different T cell epitopes (TCE). Chimeric constructs were systematically optimised with respect to length and copy number of the BCE and the nature and orientation of the TCE. Surprisingly, the induction of MV-crossreactive antibodies did not correlate with the antigenicity of the peptides. The best MV-crossreactive antibodies were obtained with TB oriented constructs containing TCEs of the MV fusion (F) protein and the BCE H236-250 (TB(15mer)) or H236-255 (TB(20mer)). In vitro virus-neutralising sera were obtained solely with the latter construct. A glycine scan showed that binding to MV depended on a defined pattern of contact residues compatible with the putative alpha helical nature of this epitope. The contact residues of the neutralising serum (S244EL-QL249) differed from those of the non- neutralising serum (S244EL246) but no unique differences in the immunoglobulin subclasses were detected. Surface plasmon resonance measurements detected a higher affinity for the neutralising serum compared to the TB(15mer) serum. These results emphasize the need of an optimal design of immunogenic peptides which cannot always be guided by the antigenicity of the peptide constructs. This study demonstrates that neutralising antibodies can be generated with peptides mimicking this helical epitope, provided that the critical contact residues are recognized with high affinity and underlines the potential of the epitope as an element of a future subunit vaccine.

Original languageEnglish
Pages (from-to)905-918
Number of pages14
JournalMolecular Immunology
Volume35
Issue number14-15
DOIs
Publication statusPublished - 1 Oct 1998
Externally publishedYes

Keywords

  • B cell epitope
  • Measles virus
  • Neutralisation
  • Synthetic peptides
  • T cell epitope

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