Peptide fibrils as a vaccine: Proof of concept.

Background: Rapid vaccine platforms development is crucial for responding to epidemics and pandemics of emerging infectious diseases, such as Ebola. This study explores the potential of peptide vaccines that self-organize into amyloid-like fibrils, aiming to enhance immunogenicity while considering safety and cross-reactivity.

Methods: We synthesized two peptides, G33 and G31, corresponding to a segment of the Ebola virus GP2 protein, with G33 known to form amyloid-like fibrils. Their toxicity was assessed in vitro using an MTT assay on MDCK and A549 cell cultures. For in vivo studies, balb/c mice were immunized with these peptides. Immunogenicity was gauged by ELISA for specific antibodies against the recombinant eGP protein. Hematological parameters were determined, and histopathological changes in organs were documented post-euthanasia.

Results: Both peptides exhibited no cytotoxicity up to 500 μg/ml. G33-immunized mice developed higher antibody titers than those receiving G31 or control, without significant alterations in hematological profiles. However, histological analysis showed periportal infiltration and lymphoid-macrophage clusters in the liver and kidneys, suggesting immune response activation. The homology between the G33 peptide and mammalian proteins poses risks of cross-reactivity.

Conclusion: The amyloid-like fibrils formed by the G33 peptide elicited a stronger immune response without significant hematological changes, underlining the feasibility of fibril-based peptide vaccines. However, the potential for autoimmune responses due to molecular mimicry warrants further investigation before clinical applications can be considered.