Identification of a conserved neutralization site in the first heptad repeat of the fusion protein of respiratory syncytial virus

Summary

A large set of monoclonal antibodies (MAbs) directed against the fusion glycoprotein complex F₁F₂ of bovine respiratory syncytial virus (BRSV) and several polyclonal sera from infected or vaccinated animals were tested in Pepscan to locate linear epitopes on the F-protein. The polyclonal sera mapped to antigenic sites that correspond exactly to known antigenic sites on the F protein of human RSV. Only the neutralizing MAb 3 could be mapped with Pepscan. MAb 3 reacted with three successive overlapping linear peptides that shared the amino acid sequence ¹⁷³STNKAVVSLS¹⁸². The sequence of this novel neutralization site is conserved in all known BRSV- and human RSV-strains and is located on the N-terminus of F₁, adjacent to the hydrophobic, putative fusion-related region. This region is probably part of a central coiled-coil stem that is structurally conserved in paramyxovirus fusion and orthomyxovirus hemagglutinin glycoproteins. This linear conserved epitope may be a potential candidate for a peptide-based vaccine which can induce neutralizing antibodies against all groups and subgroups of RSV. Furthermore, the proposed structural features of the neutralization site may aid in the design of a peptide-based vaccine.