Characterization of surface-exposed structural loops as insertion sites for foreign antigen delivery in calicivirus-derived VLP platform

Mirosława Panasiuk; Milena Chraniuk; Karolina Zimmer; Lilit Hovhannisyan; Vasil Krapchev; Grażyna Peszyńska-Sularz; Magdalena Narajczyk; Jan Węsławski; Agnieszka Konopacka; Beata Gromadzka

doi:10.3389/fmicb.2023.1111947

Characterization of surface-exposed structural loops as insertion sites for foreign antigen delivery in calicivirus-derived VLP platform

Front Microbiol. 2023 Feb 27:14:1111947. doi: 10.3389/fmicb.2023.1111947. eCollection 2023.

Authors

Mirosława Panasiuk^{1

2

3}, Milena Chraniuk^{1

2}, Karolina Zimmer^{3

4}, Lilit Hovhannisyan¹, Vasil Krapchev³, Grażyna Peszyńska-Sularz⁵, Magdalena Narajczyk⁶, Jan Węsławski^{3

7}, Agnieszka Konopacka⁸, Beata Gromadzka^{1

2

3}

Affiliations

¹ Department of In Vitro Studies, Institute of Biotechnology and Molecular Medicine, Gdańsk, Poland.
² Nano Expo Sp z.o.o, Gdańsk, Poland.
³ Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
⁴ Faculty of Health Sciences, Department of Biochemistry and Molecular Biology, University of Bielsko-Biala, Bielsko-Biala, Poland.
⁵ Tri-City Central Animal Laboratory Research and Service Center, Medical University of Gdańsk, Gdańsk, Poland.
⁶ Laboratory of Electron Microscopy, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
⁷ Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
⁸ Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland.

Abstract

Chimeric virus-like particles (cVLPs) show great potential in improving public health as they are safe and effective vaccine candidates. The capsid protein of caliciviruses has been described previously as a self-assembling, highly immunogenic delivery platform. The ability to significantly induce cellular and humoral immunity can be used to boost the immune response to low immunogenic foreign antigens displayed on the surface of VLPs. Capsid proteins of caliciviruses despite sequence differences share similar architecture with structural loops that can be genetically modified to present foreign epitopes on the surface of cVLPs. Here, based on the VP1 protein of norovirus (NoV), we investigated the impact of the localization of the epitope in different structural loops of the P domain on the immunogenicity of the presented epitope. In this study, three distinct loops of NoV VP1 protein were genetically modified to present a multivalent influenza virus epitope consisting of a tandem repeat of M2/NP epitopes. cVLPs presenting influenza virus-conserved epitopes in different localizations were produced in the insect cells and used to immunize BALB/c mice. Specific reaction to influenza epitopes was compared in sera from vaccinated mice to determine whether the localization of the foreign epitope has an impact on the immunogenicity.

Keywords: VLP platform; calicivirus; chimeric virus-like particles; foreign antigen; immunogenicity; influenza A virus; norovirus; vaccine development.