Immunological Characterization of PLGA Encapsulated mRNA Expressing Crimean-Congo Haemorrhagic Fever Virus (CCHFV) Nucleocapsid Protein (NP) [Oral Presentation]

Keskin S., Sak R., Bahadorı F., Doymaz M. Z.

17th World Immune Regulation Meeting, Zürich, İsviçre, 06 Temmuz 2023, (Tam Metin Bildiri)

  • Yayın Türü: Bildiri / Tam Metin Bildiri
  • Basıldığı Şehir: Zürich
  • Basıldığı Ülke: İsviçre
  • Bezmiâlem Vakıf Üniversitesi Adresli: Evet

Özet

Crimean-Congo Hemorrhagic Fever (CCHF) is listed as one of the most significant tick-borne viral diseases due to its extensive geographic distribution, capacity to cause epidemics, and about 30% fatality rate. The infection spreads worldwide. CCHF incidence in new geographic locations raise concerns about disease transmission. CCHF threatens global public health because to its high mortality and lack of licensed immunizations or therapies. Consequently, efficient CCHF vaccines and immunological, virological, and molecular biology studies are essential. mRNA structures have garnered interest recently due of their advantages over traditional gene transfer platforms. In this study, Poly(lactic-co-glycolic acid) (PLGA) was used to encapsulate mRNA for non-optimized small (S) segment of CCHFV Kelkit06 strain. PLGA is biodegradable and an FDA-approved formulation for drug delivery due to its regulated and prolonged release, low toxicity, and biocompatibility with tissues and cells.


In this experimental study, nucleoside modified CCHFV-NP mRNA was expressed in Huh-7 cells and its expression was confirmed by Western Blot, ELISA, and Immunofluorescence. Thus, the expression of the mRNA structure was monitored by cell culture transfections. CCHFV-NP mRNA formulated with PLGA induced humoral and cellular immune responses in Balb-C mice following intramuscular injections. Results from in-house ELISA and cellular immune response tests indicated that CCHFV-NP mRNA+PLGA elicits CCHFV-NP-specific immune responses. mRNA-PLGA constructs combined the safety of a transient carrier and the inducing ability of nucleotide vaccines with an effective immune response. Thus, the study demonstrates the development of an effective vaccine candidate that can be investigated against CCHF, one of the fearsome viral diseases. Performed immunological characterization studies show that CCHFV-NP-based mRNA-PLGA construct mediates the immunological response in mice. In conclusion, we evaluated a new approach to CCHFV immunology by introducing an mRNA platform that could be considered an effective and safe way to combat this disease in future experiments.