Peptides for Anti-Ebolavirus Vaccines

Background: Two main factors can affect the development of ebolavirus immunotherapeutics: the vast peptide commonality between ebolavirus and human proteins, and the high rate of spontaneous mutation of ebolavirus within its human host. Indeed, the viral versus human peptide overlap may represent a relevant source of autoimmune crossreactions following vaccination, while ebolavirus genome mutations can limit and/or nullify a vaccine response. Methods: Aiming at defining safe and effective peptide-based vaccines to fight ebola disease, this study analyzed a recently described Ebola virus isolate (Hoenen et al., Emerging Infect Dis 2016, 22, 331) for sequences not shared with the human proteome and conserved among ebolaviruses. Results: Using the pentapeptide as a minimal immune determinant, it was found that: 1) only 6.6% of the 4865 pentapeptides present in the Ebola virus isolate proteins are unique to the virus; 2) only 55 of the unique viral pentapeptides are conserved among 251 proteomes derived from the four ebolavirus species that may affect humans; and 3) none of the unique peptide signatures that mark Ebola virus isolate glycoprotein are 100% conserved. Conclusions: The present findings pose the basis for the construction of viral polypeptide antigens able to induce non-crossreactive, specific and broadly protective immune responses against ebolavirus, and warn against immune therapeutic/preventive approaches exclusively focused on glycoprotein epitope(s).