Abstract

Background. Although rare, adverse events may associate with anti-poliovirus vaccination thus possibly hampering global polio eradication worldwide. Objective. To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate. Methods. Proteins from poliovirus type 1, strain Mahoney, were analyzed for amino acid sequence identity to the human proteome at the pentapeptide level, searching for sequences that (1) have zero percent of identity to human proteins, (2) are potentially endowed with an immunologic potential, and (3) are highly conserved among poliovirus strains. Results. Sequence analyses produced a set of consensus epitopic peptides potentially able to generate specific anti-polio immune responses exempt from cross-reactivity with the human host. Conclusion. Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination.

Highlights

  • Vaccine-associated paralytic poliomyelitis (VAPP) [1] is the consequence of the replication of vaccine-derived polioviruses (VDPVs) that originate by genetic mutations from the strain contained in the oral polio vaccine (OPV)

  • Pursuing the objectives of overcoming the difficulties posed by the PV tendency to mutate and eliminating the viral reactivation-related VAPP in order to contribute to the global eradication of poliomyelitis, here we examine PV1 Mahoney polyprotein primary sequence and describe a set of pentapeptides uniquely owned by PV1, endowed with immunologic potential, and conserved among 43 PV strains

  • Consensus peptide sequences were defined by ClustalW multialignment analysis [24] of sequences from 43 PV strains retrieved from UniProt database on the basis of the following characteristics: (1) described in scientific literature; (2) corresponding to the entire PV polyprotein; (3) derived from PV1 and PV3; (4) derived from PV variants isolated from VAPP or acute flaccid paralysis (AFP) patients or from immunocompromised patients with residual paralysis

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Summary

Introduction

Vaccine-associated paralytic poliomyelitis (VAPP) [1] is the consequence of the replication of vaccine-derived polioviruses (VDPVs) that originate by genetic mutations from the strain contained in the oral polio vaccine (OPV). It has been observed that reduction of exposure to a live attenuated virus such as that contained in OPV will inevitably lead to a decrease in herd immunity to a live microorganism and to natural boosters [7] Such considerations, along with recent PV infection outbreaks, further complicate the issue of polio eradication [8]. To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate. Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination

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