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Volume 74, Issue 12

Conformational constraints of conserved neutralizing epitopes from a major antigenic area of human respiratory syncytial virus fusion glycoprotein Free

Abstract

To study the conformational requirements of epitopes from a conserved antigenic area (area II) of respiratory syncytial (RS) virus fusion (F) glycoprotein, peptides of increasing length containing amino acids essential for these epitopes were synthesized. The synthetic peptides were tested for binding to a panel of neutralizing monoclonal antibodies (MAbs) for this area as well as to rabbit hyperimmune and human convalescent antisera. Antibody binding was dependent on peptide length; thus, a 61-residue peptide spanning amino acids 215 to 275 of the F subunit (peptide F215–275) reacted with more antibodies than a shorter (41-residue) peptide F235–275, and this one with more than the (21-residue) peptide F255–275. Most human convalescent sera contained antibodies that reacted with peptides F215–275 and F235–275 but failed to react with F255–275. The results of antibody binding could be related to the structure adopted by the peptides in solution, as determined by circular dichroism spectroscopy and susceptibility of peptides to trypsin digestion. Pretreatment of peptide F215–275 with SDS abolished reactivity with certain MAbs, supporting the notion that higher order structures were needed for antibody binding. High titre anti-peptide antisera were induced in rabbits inoculated with the peptides; however, these sera failed to react with the native F molecule. In mice, only the largest F215–275 peptide induced an anti-peptide response, but their sera reacted poorly with the native F protein and the animals were not protected against an RS virus challenge. These results illustrate the potential use of synthetic peptides in studies of the F protein physical and antigenic structures as well as the problems in designing synthetic RS virus vaccines.

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© Journal of General Virology 1993
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1993-12-01
2024-04-25
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Conformational constraints of conserved neutralizing epitopes from a major antigenic area of human respiratory syncytial virus fusion glycoprotein
J. Gen. Virol. 74, 2567 (1993); https://doi.org/10.1099/0022-1317-74-12-2567
/content/journal/jgv/10.1099/0022-1317-74-12-2567
/content/journal/jgv/10.1099/0022-1317-74-12-2567
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