Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine
Self-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. Infectious Hematopoietic Necrosis virus (IHNV) is the causative agent of the WOAH-liste...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1346512/full |
| _version_ | 1797341228166021120 |
|---|---|
| author | Sohrab Ahmadivand Zeljka Krpetic Merce Márquez Martínez Merce Márquez Martínez Marlid Garcia-Ordoñez Nerea Roher Nerea Roher Dušan Palić |
| author_facet | Sohrab Ahmadivand Zeljka Krpetic Merce Márquez Martínez Merce Márquez Martínez Marlid Garcia-Ordoñez Nerea Roher Nerea Roher Dušan Palić |
| author_sort | Sohrab Ahmadivand |
| collection | DOAJ |
| description | Self-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. Infectious Hematopoietic Necrosis virus (IHNV) is the causative agent of the WOAH-listed IHN diseases for which there are currently no therapeutic treatments and no globally available commercial vaccine. In this study, by genetically fusing the virus glycoprotein to the H. pylori ferritin as a scaffold, we constructed a self-assembling IHNV nanovaccine (FerritVac). Despite the introduction of an exogenous fragment, the FerritVac NPs show excellent stability same as Ferritin NPs under different storage, pH, and temperature conditions, mimicking the harsh gastrointestinal condition of the virus main host (trout). MTT viability assays showed no cytotoxicity of FerritVac or Ferritin NPs in zebrafish cell culture (ZFL cells) incubated with different doses of up to 100 µg/mL for 14 hours. FerritVac NPs also upregulated expression of innate antiviral immunity, IHNV, and other fish rhabdovirus infection gene markers (mx, vig1, ifit5, and isg-15) in the macrophage cells of the host. In this study, we demonstrate the development of a soluble recombinant glycoprotein of IHNV in the E. coli system using the ferritin self-assembling nanoplatform, as a biocompatible, stable, and effective foundation to rescue and produce soluble protein and enable oral administration and antiviral induction for development of a complete IHNV vaccine. This self-assembling protein nanocages as novel vaccine approach offers significant commercial potential for non-mammalian and enveloped viruses. |
| first_indexed | 2024-03-08T10:14:49Z |
| format | Article |
| id | doaj.art-a4a4973abd044a879be706a7a80725c5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T10:14:49Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a4a4973abd044a879be706a7a80725c52024-01-29T04:40:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.13465121346512Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccineSohrab Ahmadivand0Zeljka Krpetic1Merce Márquez Martínez2Merce Márquez Martínez3Marlid Garcia-Ordoñez4Nerea Roher5Nerea Roher6Dušan Palić7Faculty of Veterinary Medicine, Ludwig-Maximilians University Munich, Munich, GermanyBiomedical Research Centre, School of Science Engineering and Environment, University of Salford, Salford, United KingdomInstitute of Biotechnology and Biomedicine (IBB), Universitat Autònoma de Barcelona, Barcelona, SpainCIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, SpainInstitute of Biotechnology and Biomedicine (IBB), Universitat Autònoma de Barcelona, Barcelona, SpainInstitute of Biotechnology and Biomedicine (IBB), Universitat Autònoma de Barcelona, Barcelona, SpainCIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, SpainFaculty of Veterinary Medicine, Ludwig-Maximilians University Munich, Munich, GermanySelf-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. Infectious Hematopoietic Necrosis virus (IHNV) is the causative agent of the WOAH-listed IHN diseases for which there are currently no therapeutic treatments and no globally available commercial vaccine. In this study, by genetically fusing the virus glycoprotein to the H. pylori ferritin as a scaffold, we constructed a self-assembling IHNV nanovaccine (FerritVac). Despite the introduction of an exogenous fragment, the FerritVac NPs show excellent stability same as Ferritin NPs under different storage, pH, and temperature conditions, mimicking the harsh gastrointestinal condition of the virus main host (trout). MTT viability assays showed no cytotoxicity of FerritVac or Ferritin NPs in zebrafish cell culture (ZFL cells) incubated with different doses of up to 100 µg/mL for 14 hours. FerritVac NPs also upregulated expression of innate antiviral immunity, IHNV, and other fish rhabdovirus infection gene markers (mx, vig1, ifit5, and isg-15) in the macrophage cells of the host. In this study, we demonstrate the development of a soluble recombinant glycoprotein of IHNV in the E. coli system using the ferritin self-assembling nanoplatform, as a biocompatible, stable, and effective foundation to rescue and produce soluble protein and enable oral administration and antiviral induction for development of a complete IHNV vaccine. This self-assembling protein nanocages as novel vaccine approach offers significant commercial potential for non-mammalian and enveloped viruses.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1346512/fullferritin nanoparticlesIHNVself-assembling vaccinefish virusesZFL cellsmacrophages |
| spellingShingle | Sohrab Ahmadivand Zeljka Krpetic Merce Márquez Martínez Merce Márquez Martínez Marlid Garcia-Ordoñez Nerea Roher Nerea Roher Dušan Palić Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine Frontiers in Immunology ferritin nanoparticles IHNV self-assembling vaccine fish viruses ZFL cells macrophages |
| title | Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine |
| title_full | Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine |
| title_fullStr | Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine |
| title_full_unstemmed | Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine |
| title_short | Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine |
| title_sort | self assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine |
| topic | ferritin nanoparticles IHNV self-assembling vaccine fish viruses ZFL cells macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1346512/full |
| work_keys_str_mv | AT sohrabahmadivand selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT zeljkakrpetic selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT mercemarquezmartinez selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT mercemarquezmartinez selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT marlidgarciaordonez selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT nerearoher selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT nerearoher selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine AT dusanpalic selfassemblingferritinnanoplatformforthedevelopmentofinfectioushematopoieticnecrosisvirusvaccine |