Immunogenicity and Neutralization of Recombinant Vaccine Candidates Expressing F and G Glycoproteins against Nipah Virus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Recombinant Vaccine Design and Phylogenetic Analysis
2.3. Plasmid Preparation and Expression of Recombinant Proteins
2.4. SDS-PAGE and Western Blot
2.5. Immunization of Mice
2.6. Enzyme-Linked Immunosorbent Assay
2.7. Generation of Pseudovirus Expressing Nipah Virus F or G Glycoproteins
2.8. Pseudovirus-Based Neutralization Assay
2.9. Statistical Analysis
3. Results
3.1. Nipah Virus Strain Selection
3.2. Design of NiV-F/G Vaccine Candidates
3.3. Expression of Recombinant NiV Proteins
3.4. Immunogenity of Recombinant NiV Proteins
3.5. Neutralization Efficacy of Recombinant NiV Proteins
3.6. Immunogenicity of Bivalent and Trivalent NiV Vaccines Using Different Adjuvants
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Name | Target Sequence | Structure | Mutation | Tag | Multimeric Domain | Accession Number |
---|---|---|---|---|---|---|
NiV_Fmo | F | Monomer | I114C, L104C, S191P, L172F | 6× his | - | In this study (OR947674) |
NiV_Ftri | F | Trimer | I114C, L104C, S191P, L172F | 6× his | GCN4 | |
NiV_GMYm | G | Monomer | - | 6× his | - | In this study (OR947675) |
NiV_GBDm | G | Monomer | - | 6× his | - | In this study (OR947676) |
NiV_GMYtet | G | Tetramer | - | 6× his | - | In this study (OR947675) |
NiV_GBDtet | G | Tetramer | - | 6× his | - | In this study (OR947676) |
C_Ftri_GMYtet | F + G | Chimeric † | - | 6× his | GCN4 | |
C_Ftri_GBDtet | F + G | Chimeric † | - | 6× his | GCN4 |
Group | Vaccine | Dose | Description | Target | Route | Sample Size (n) |
---|---|---|---|---|---|---|
1 | PBS | 20 μg | Control | IM | 8 | |
2 | Fm | 20 μg | F monomer | F | IM | 8 |
3 | GMYm | 20 μg | GMY monomer | GMY | IM | 8 |
4 | GBDm | 20 μg | GBD monomer | GBD | IM | 8 |
5 | Fm + GMYm | 20 μg + 20 μg | F monomer + GMY monomer | F, GMY | IM | 8 |
6 | Fm + GBDm | 20 μg + 20 μg | F monomer + GMY monomer | F, GBD | IM | 8 |
7 | Ftri | 20 μg | F trimer | F | IM | 8 |
8 | GMYtet | 20 μg | GMY tetramer | GMY | IM | 8 |
9 | GBDtet | 20 μg | GBD tetramer | GBD | IM | 8 |
10 | Ftri + GMYtet | 20 μg + 20 μg | F trimer + GMY tetramer | F, GMY | IM | 8 |
11 | Ftri + GBDtet | 20 μg + 20 μg | F trimer + GBD tetramer | F, GBD | IM | 8 |
12 | c-Ftri-GMYtet | 20 μg | Chimeric F trimer-GMY tetramer | F, GMY | IM | 8 |
13 | c-Ftri-GBDtet | 20 μg | Chimeric F trimer- GBD tetramer | F, GBD | IM | 8 |
14 | GMYm + GBDm | 20 μg + 20 μg | GMY monomer + GBD monomer | GMY, GBD | IM | 8 |
15 | Fm + GMYm + GBDm | 20 μg + 20 μg + 20 μg | F monomer + GMY monomer + GBD monomer | F, GMY, GBD | IM | 8 |
16 | GMYtet + GBDtet | 20 μg + 20 μg | GMY tetramer + GBD tetramer | GMY, GBD | IM | 8 |
17 | Ftri + GMYtet + GBDtet | 20 μg + 20 μg + 20 μg | F trimer + GMY tetramer + GBD tetramer | F, GMY, GBD | IM | 8 |
18 | c-Ftri-GMYtet + c-Ftri-GBDtet | 20 μg + 20 μg | Chimeric F trimer-GMY tetramer + Chimeric F trimer- GBD tetramer | F, GMY, GBD | IM | 8 |
Group | Vaccine | NiV-Vaccine | Dose | Adjuvant | Route | Sample Size (n) |
---|---|---|---|---|---|---|
1 | PBS | IM | 6 | |||
2 | G-Phos | GMYtet + GBDtet | 20 µg + 20 µg | Phos | IM | 6 |
3 | G-Alum | GMYtet + GBDtet | 20 µg + 20 µg | Alum | IM | 6 |
4 | G-MPLA | GMYtet + GBDtet | 20 µg + 20 µg | MPLA | IM | 6 |
5 | G-AS03 | GMYtet + GBDtet | 20 µg + 20 µg | AS03 | IM | 6 |
6 | G-Vax | GMYtet + GBDtet | 20 µg + 20 µg | Vax | IM | 6 |
7 | FG-Phos | Ftri + GMYtet + GBDtet | 20 µg + 20 µg + 20 µg | Phos | IM | 6 |
8 | FG-Alum | Ftri + GMYtet + GBDtet | 20 µg + 20 µg + 20 µg | Alum | IM | 6 |
9 | FG-MPLA | Ftri + GMYtet + GBDtet | 20 µg + 20 µg + 20 µg | MPLA | IM | 6 |
10 | FG-AS03 | Ftri + GMYtet + GBDtet | 20 µg + 20 µg + 20 µg | AS03 | IM | 6 |
11 | FG-Vax | Ftri + GMYtet + GBDtet | 20 µg + 20 µg + 20 µg | Vax | IM | 6 |
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Moon, S.Y.; Flores, R.A.; Yim, M.S.; Lim, H.; Kim, S.; Lee, S.Y.; Lee, Y.-k.; Kim, J.-O.; Park, H.; Bae, S.E.; et al. Immunogenicity and Neutralization of Recombinant Vaccine Candidates Expressing F and G Glycoproteins against Nipah Virus. Vaccines 2024, 12, 999. https://doi.org/10.3390/vaccines12090999
Moon SY, Flores RA, Yim MS, Lim H, Kim S, Lee SY, Lee Y-k, Kim J-O, Park H, Bae SE, et al. Immunogenicity and Neutralization of Recombinant Vaccine Candidates Expressing F and G Glycoproteins against Nipah Virus. Vaccines. 2024; 12(9):999. https://doi.org/10.3390/vaccines12090999
Chicago/Turabian StyleMoon, Seo Young, Rochelle A. Flores, Min Su Yim, Heeji Lim, Seungyeon Kim, Seung Yun Lee, Yoo-kyoung Lee, Jae-Ouk Kim, Hyejin Park, Seong Eun Bae, and et al. 2024. "Immunogenicity and Neutralization of Recombinant Vaccine Candidates Expressing F and G Glycoproteins against Nipah Virus" Vaccines 12, no. 9: 999. https://doi.org/10.3390/vaccines12090999