A novel strategy to mimic discontinuous protective epitopes using a synthetic scaffold.
Although vaccines have been used for a long time and different types of vaccines have been developed, as yet no fully synthetic vaccines have been produced. The production of fully synthetic vaccines has probably not been realized so far due to the structural limitations of linear synthetic peptides to mimic the native shape of protein fragments which is often needed to induce protective antibodies. In this report we used the Bordetella pertussis protein pertactin as a model and show that a novel synthetic scaffold can be used to mimic structurally defined epitopes by confined presentation of several different peptide arms. Guided by modelling a construct was synthesized that induced protective antibodies directed towards a discontinuous epitope. This approach opens up the possibility to the design of new and fully synthetic vaccines that can induce protective antibodies.
Hijnen
Marcel
M
Laboratory for Vaccine Preventable Diseases, National Institute of Public Health and the Environment, Antonie van Leeuwenhoeklaan 1, PO Box 1, Bilthoven, The Netherlands.
van Zoelen
Dirk J
DJ
Chamorro
Cristina
C
van Gageldonk
Pieter
P
Mooi
Frits R
FR
Berbers
Guy
G
Liskamp
Rob M J
RM
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D018716:Molecular Mimicry / Q000276:immunology*; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D010566:Virulence Factors, Bordetella / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D010566:Virulence Factors, Bordetella; C068929:pertactin