Neutralization of MERS coronavirus through a scalable nanoparticle vaccine
MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic...
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| Vydáno v: | npj vaccines Ročník 6; číslo 1; s. 107 - 9 |
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24.08.2021
Nature Publishing Group Nature Portfolio |
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| Abstract | MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMV
TT
-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMV
TT
-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within
E. coli
upon expression. mCuMV
TT
-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans. |
|---|---|
| AbstractList | MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans.MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans. MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMV TT -VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMV TT -MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMV TT -MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans. MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans. Abstract MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans. |
| ArticleNumber | 107 |
| Author | Tars, Kaspars Dermime, Said Mohsen, Mona O. Vogel, Monique Rothen, Dominik Balke, Ina Zeltina, Vilija Inchakalody, Varghese Zeltins, Andris Bachmann, Martin F. Martina, Byron Nasrallah, Gheyath Gharailoo, Zahra |
| Author_xml | – sequence: 1 givenname: Mona O. surname: Mohsen fullname: Mohsen, Mona O. email: mona.mohsen@dbmr.unibe.ch organization: Department of BioMedical Research, University of Bern, Department of Immunology RIA, University Hospital Bern, Translational Cancer Research Facility and Clinical Trials Unit, Interim Translational Research Institute, Hamad Medical Corporation – sequence: 2 givenname: Dominik surname: Rothen fullname: Rothen, Dominik organization: Department of BioMedical Research, University of Bern, Department of Immunology RIA, University Hospital Bern – sequence: 3 givenname: Ina orcidid: 0000-0002-5171-7744 surname: Balke fullname: Balke, Ina organization: Latvian Biomedical Research & Study Centre, Ratsupites iela1 – sequence: 4 givenname: Byron surname: Martina fullname: Martina, Byron organization: Erasmus Medical Center, department of Viroscience, Artemis Bio-Support – sequence: 5 givenname: Vilija surname: Zeltina fullname: Zeltina, Vilija organization: Latvian Biomedical Research & Study Centre, Ratsupites iela1 – sequence: 6 givenname: Varghese surname: Inchakalody fullname: Inchakalody, Varghese organization: Translational Cancer Research Facility and Clinical Trials Unit, Interim Translational Research Institute, Hamad Medical Corporation – sequence: 7 givenname: Zahra surname: Gharailoo fullname: Gharailoo, Zahra organization: Department of BioMedical Research, University of Bern, Department of Immunology RIA, University Hospital Bern – sequence: 8 givenname: Gheyath orcidid: 0000-0001-9252-1038 surname: Nasrallah fullname: Nasrallah, Gheyath organization: Research Complex, Qatar University – sequence: 9 givenname: Said orcidid: 0000-0002-5526-7496 surname: Dermime fullname: Dermime, Said organization: Translational Cancer Research Facility and Clinical Trials Unit, Interim Translational Research Institute, Hamad Medical Corporation – sequence: 10 givenname: Kaspars surname: Tars fullname: Tars, Kaspars organization: Latvian Biomedical Research & Study Centre, Ratsupites iela1 – sequence: 11 givenname: Monique surname: Vogel fullname: Vogel, Monique organization: Department of BioMedical Research, University of Bern, Department of Immunology RIA, University Hospital Bern – sequence: 12 givenname: Andris surname: Zeltins fullname: Zeltins, Andris organization: Latvian Biomedical Research & Study Centre, Ratsupites iela1 – sequence: 13 givenname: Martin F. orcidid: 0000-0003-4370-2099 surname: Bachmann fullname: Bachmann, Martin F. organization: Department of BioMedical Research, University of Bern, Department of Immunology RIA, University Hospital Bern, Jenner Institute, Nuffield Department of Medicine, University of Oxford, International Immunology Centrer, Anhui Agricultural University |
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| CitedBy_id | crossref_primary_10_3390_vaccines12060661 crossref_primary_10_3389_fbioe_2022_867119 crossref_primary_10_3389_fmicb_2023_1154990 crossref_primary_10_1111_all_15704 crossref_primary_10_1136_jitc_2022_004643 crossref_primary_10_3390_vaccines10020307 crossref_primary_10_1111_all_15311 crossref_primary_10_1016_j_vetmic_2025_110655 crossref_primary_10_3389_fimmu_2022_864718 crossref_primary_10_1016_j_nano_2022_102584 crossref_primary_10_3390_nano13091467 crossref_primary_10_1038_s41423_022_00897_8 |
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| SubjectTerms | 631/250 631/250/590/2294 Biomedical and Life Sciences Biomedicine E coli Hepatitis Infectious Diseases Medical Microbiology Middle East respiratory syndrome Neutralization Public Health Toxins Vaccine Vaccines Virology |
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| Title | Neutralization of MERS coronavirus through a scalable nanoparticle vaccine |
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