Heterotypic protection induced by synthetic peptides corresponding to three serotypes of foot-and-mouth disease virus

217

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease. Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented. Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined. None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40%. Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus. In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified. This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo. In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy. Possible modifications of the vaccine formulations to increase protective activity are discussed.

Section: Discussionmentioning

confidence: 99%

A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants

Taboga¹,

Tami²,

Carrillo³

et al. 1997

217

“…In a previous paper, we addressed the question of the specificity of the response to synthetic FMD peptides and demonstrated that, contrary to expectations, each of the A, C, and 0 serotype peptides conferred heterologous as well as homologous protection of guinea pigs (8). From the available data, it was not possible to identify the sequence or sequences of each peptide responsible for heterologous protection, although it was speculated that the highly conserved R-G-D tripeptide within the 141-158 region might be involved.…”

mentioning

confidence: 84%

“…Peptides. The following peptides were synthesized by conventional solid-phase methods and purified to near homogeneity by reverse-phase chromatography as previously described (8).…”

Section: Materuils and Methodsmentioning

confidence: 99%

“…Residues 200 to 213 represent the C terminus of VP1 which, within the virus, is closely associated with the G-H loop of an adjacent promoter (1). When delivered in an oil adjuvant, the composite peptide and a similar peptide based on the sequence of the VP1 of the A24 Cruzeiro strain of FMDV were capable of protecting cattle against intradermolingual challenge with highly virulent homologous virus (6,8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Doel

Staple

et al. 1992

Self Cite

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.

“…Specifically, Krebs et al (20) have shown that swine vaccinated with peptides based on the type 0 G-H loop developed FMD following challenge, and an antigenic variant isolated from one animal was not neutralized by antipeptide sera. Vaccination-challenge studies using synthetic peptides have also failed to demonstrate complete protection in cattle, offering further evidence of failure of vaccines presenting only a single antigenic site (12,13).…”

mentioning

confidence: 99%

Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies and protective immunity to multiple serotypes of FMDV

Rieder

Baxt

Liu

et al. 1994

The G-H loop of VP1 (residues 132 to 159) of foot-and-mouth disease virus (FMDV) is a prominent feature on the virion surface and has an important role in vaccine efficacy, generation of antigenic variants, and cell binding. Using an infectious cDNA of FMDV, we have constructed serotype A viruses in which the G-H loop has been substituted with the homologous sequences from serotype 0 or C. These chimeric viruses replicated to high titer and displayed plaque morphologies similar to those of wild-type viruses, demonstrating that the functions provided by the loop can be readily exchanged between serotypes. Monoclonal antibody analyses showed that epitopes contained within the loop were transferred to the chimeras and that epitopes encoded by the type A backbone were maintained. Chemically inactivated vaccines prepared from chimeric viruses induced antibodies in guinea pigs that neutralized both type A and either type 0 or type C viruses. Swine inoculated with the A/C chimera vaccine also produced cross-reactive antibodies, were protected from challenge with the type A virus, and partially protected against challenge with type C. These studies emphasize the importance of epitopes outside of the G-H loop in protective immunity in swine, which is a natural host of FMDV.