The availability of platforms that enable the rapid development of a vaccine to protect against pathogens causing local outbreaks is an urgent task, given the ongoing threats of epidemics and pandemics caused by new zoonotic infections. One of these pathogens is the Ebola virus (Malik et al., 2023). The experience gained from the pandemic caused by SARS-Cov2 has demonstrated that elaboration of platforms for vaccine development allows for a quick response to emerging challenges and facilitates the production of a vaccine against a completely new pathogen (Dolzhikova et al., 2017; Tukhvatulin et al., 2022). A flexible and rapidly deployable platform is the peptide vaccine platform (Skwarczynski and Toth, 2016; Francis, 2018).

However, the use of peptide vaccines presents several challenges, including low immunogenicity and the need to use adjuvants or create chimeric proteins to adapt the antigen structure for recognition by the human immune system (Herst et al., 2020; Egorov et al., 2023). In this study, we propose an approach to enhance the immunogenicity of peptide vaccines by utilizing the self-organization of peptides into spatial structures necessary for triggering an immune response. One such approach involves the formation of a quaternary structure through amyloid-like self-organization. We hypothesize that the induction of fibrillogenesis is specific, and the presence of immunogenic components of the virus that have formed fibrils cannot induce fibril formation by human proteins in the absence of homology between the antigen and host proteins (Krebs et al., 2004; Iadanza et al., 2018). To test this hypothesis and develop a vaccine capable of inducing the formation of virus-neutralizing antibodies, it is necessary to select a surface antigen with the following properties: (1) it must be located in a critical region, the interaction of antibodies with which leads to virus neutralization; (2) it must be capable of forming amyloid-like fibrils.

In a previous study (Herst et al., 2020), a spatial epitope of the Ebola virus GP protein was identified through epitope screening, and antibodies targeting this epitope were found to have a neutralizing effect. Additionally, our previous research demonstrated that a component of this epitope, the non-glycosylated GP region, is capable of forming amyloid-like fibrils (Egorov et al., 2016). Briefly, we found that a peptide matching the primary structure of the viral GP protein fragment can exist in soluble and fibrillar forms, depending on the amino acid residue at the C-terminus. A peptide with a Q at the C-terminus formed fibrils, while a peptide with a G at the C-terminus did not. This system allowed us to test the concept of enhancing the immunogenicity of potential peptide vaccines through the formation of amyloid-like fibrils by antigens. Therefore, in this study, we aimed to determine (1) whether the peptide contained in fibrils would induce the formation of immunoglobulins G to whole GP better than the peptide in soluble form, and (2) whether the introduction of fibrils into a model animal would lead to acute toxicity.