Title : Homology Analysis of MPXV and VACV Peptides Underscores the Need to Consider Both MPXV Clades for Vaccine Development
Abstract:
Background: The mpox virus (MPXV) is a zoonotic disease that gained worldwide attention with the 2022 global outbreak. Current vaccination and post-exposure prophylaxis against MPXV consists of live vaccinia virus-based vaccines originally developed against smallpox. This study explores the potential for the development of peptide-based vaccines, effective against VARV, VACV, and MPXV, which could offer the advantage of fewer contraindications, inexpensive manufacturing, and better distribution logistics.
Methods: Vaccinia-derived HLA class I and class II peptide sequences, previously identified by our group through mass spectrometry and bioinformatics approaches and characterized for their immunogenic properties, were analyzed for homology with MPXV clades I and II. Our study aimed to evaluate these vaccinia-derived peptides and their potential relevance for inducing MPXV-specific immunity, focusing on conserved sequences that could elicit cross-reactive protective immune responses across both clades.
Results: Of 152 vaccinia peptides analyzed, 93 (61.2%) demonstrated 100% homology to both MPXV clades. Key immunogenic vaccinia peptides elicited positive responses in vitro in humans and in vivo in mice, with many showing cross-reactivity to both MPXV clades. Notably, 7% of MPXV sequences demonstrated divergence between clades, but most peptides demonstrated conservation, indicating potential for cross-protection.
Conclusion: This study highlights the importance of considering both MPXV clades when selecting immunogenic peptides for peptide-based vaccine development, as sequence variations exist between them. Nonetheless, the high homology between immunogenic VACV and MPXV peptides suggests the potential for developing a cross-protective vaccine for mpox, which could be a valuable tool for MPXV outbreaks and global vaccine distribution.
