Epitopes described in "Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus."

Reference
Article Authors:Jason S McLellan; Bruno E Correia; Man Chen; Yongping Yang; Barney S Graham; William R Schief; Peter D Kwong
Article Title:Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.
Reference Detail
Reference ID:1022078
Abstract:Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required.
Date:2011
Reference Type:Literature
PubMed ID:21549714
Journal:J Mol Biol
Journal Volume:409
Article Pages:853-66
Journal ISSN:1089-8638
Article Chemical List:Antibodies, Monoclonal;Antibodies, Monoclonal, Humanized;Epitopes;Staphylococcal Protein A;motavizumab
Article MeSH List:Amino Acid Sequence; Antibodies, Monoclonal(immunology); Antibodies, Monoclonal, Humanized; Calorimetry; Cell Line; Circular Dichroism; Epitopes(chemistry; immunology); Humans; Models, Molecular; Molecular Sequence Data; Respiratory Syncytial Viruses(immunology); Staphylococcal Protein A(chemistry)
Curation Last Updated:2014-07-16 22:47:28