Serological prospects for peptide vaccines against foot-and-mouth disease virus

Area of Science:

• Virology
• Immunology
• Biochemistry

Background:

• Foot-and-mouth disease virus (FMDV) poses a significant threat to livestock globally.
• The VP1 protein is a key target for neutralizing antibodies due to its surface-exposed location.
• Current FMDV vaccines often elicit responses to whole virions, which may not cover all emergent strains.

Purpose of the Study:

• To investigate the potential of synthetic peptides derived from FMDV VP1 protein as broader neutralizing agents.
• To explore how modifications to peptide sequences affect the breadth of antibody neutralization.
• To assess the protective efficacy of peptide-induced antibodies in a challenge model.

Main Methods:

• Synthesis of peptides corresponding to FMDV VP1 sequences (141-160).
• Generation of antipeptide sera and anti-virion sera for neutralization assays.
• Testing sera against a panel of FMDV type O isolates and other types.
• Amino acid substitutions within peptides to assess impact on neutralization specificity.
• In vivo protection studies using immunized guinea pigs challenged with FMDV.

Main Results:

• Antibodies to the FMDV VP1 (141-160) peptide neutralized a wider range of type O isolates compared to anti-virion serum.
• Extending the peptide sequence reduced neutralization breadth, while using non-contiguous sequences increased it.
• A specific amino acid substitution (L to S at position 148) in the peptide elicited antibodies that neutralized both type O and type A FMDV.
• Guinea pigs immunized with the modified peptide were protected against challenge with both FMDV types.
• Attempts to generate variant viruses resistant to antipeptide antibodies showed low frequency, with potential contributions from mutations outside the targeted peptide sequence.

Conclusions:

• Synthetic peptides from FMDV VP1 can elicit broadly neutralizing antibodies, exceeding the performance of traditional anti-virion sera.
• Strategic design and modification of peptide epitopes, including specific amino acid substitutions, can significantly enhance neutralization breadth and cross-reactivity.
• Peptide-based vaccines hold promise for improved FMDV control, potentially offering protection against multiple serotypes and overcoming limitations of current vaccines.