Cross-reactive and serotype-specific antibodies against foot-and-mouth disease virus generated by different regions of the same synthetic peptide

Abstract

Synthetic peptides based on the VP1 proteins of two serotypes of foot-and-mouth disease virus (FMDV) and having the general formula C-C-(200-213)-P-P-S-(141-158)-P-C-G induce heterologous as well as homologous protection against challenge. Substitution of the sequence consisting of residues 200 to 213 (200-213 sequence) with a second copy of the homologous 141-158 sequence (i.e., homodimers) resulted in failure of either serotype peptide to protect heterologously. The antiviral and antipeptide titers of sera from guinea pigs immunized with the homodimeric 141-158 peptides showed serotype specificity and, with the data from the heterodimeric peptide vaccines, suggested that the C-terminal 141-158 sequence was more effectively recognized by the immune system than the N-terminal sequence. Whereas heterologous antiviral titers as measured by enzyme-linked immunosorbent assay and virus neutralization tests have not been observed with sera from cross-protected animals, epitope-mapping studies established that there was heterologous recognition of an octapeptide within the 200-213 sequence. That the 200-213 sequence was required for the induction of heterologous protection was also confirmed with a number of peptides, including hybrids based on the 200-213 sequence of one virus and the 141-158 sequence of a second virus. Thus, peptides of the general formula given above induce serotype-specific and serotype-cross-reactive protective antibodies and are unique in their induction of significant levels of heterologous protection, a property which has never been reported for whole FMDV vaccines.

An antibody- and synthetic peptide-defined rubella virus E1 glycoprotein neutralization domain

“…Several investigators have reported the ability of selected synthetic peptides to induce neutralizing antibody responses to a limited number of animal viruses (6,7,26,32,34). Unfortunately, in some instances the critical sequences required for antibody induction appear to lie in regions of the virus that are quite variable between different virus isolates and strains, limiting the potential usefulness of these peptides as synthetic antigens or as candidate vaccines (8,20,21,54). Sequence data available for several wild-type and vaccine strains of RV suggest that the region of RV represented by SP15 is well conserved.…”

Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health

“…Linear peptides reproducing this loop from various FMDV serotypes induced nAbs in mice and guinea pigs [ 122 ] and achieved limited protection in swine [ 79 ]. Further work involved chimeric peptides that juxtaposed two antigenic sites, e.g., the G–H loop and the C-terminus of VP1, in linear fashion, also inducing nAbs [ 73 ] and modest protection in swine [ 123 ] and cattle [ 124 , 125 ]. Another linear construction, the ACT peptide, integrated site A (G–H loop of VP1), plus the VP1 C-terminus, plus a T-cell epitope [VP1(21–40)] identified in cattle [ 82 , 86 ], again affording partial protection in a large-scale vaccination trial.…”

Biosensor characterization of antigenic site A of foot-and-mouth disease virus presented in different vector systems

“…When sites A and C were joined in the same peptide and used for immunization, the constructs were able to protect cattle against infection [11]. Doel and colleagues [12] synthesized a series of chimeric peptides in which sites A and C originated from either serotype A or serotype O of the virus and they demonstrated that these peptides could protect guinea pigs against infection with both serotypes A and O.…”