論文 - 詳細
| RRC ID | 66180 |
|---|---|
| 著者 | Maeda DLNF, Tian D, Yu H, Dar N, Rajasekaran V, Meng S, Mahsoub HM, Sooryanarain H, Wang B, Heffron CL, Hassebroek A, LeRoith T, Meng XJ, Zeichner SL. |
| タイトル | Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
As the coronavirus disease 2019 (COVID-19) pandemic rages on, it is important to explore new evolution-resistant vaccine antigens and new vaccine platforms that can produce readily scalable, inexpensive vaccines with easier storage and transport. We report here a synthetic biology-based vaccine platform that employs an expression vector with an inducible gram-negative autotransporter to express vaccine antigens on the surface of genome-reduced bacteria to enhance interaction of vaccine antigen with the immune system. As a proof-of-principle, we utilized genome-reduced Escherichia coli to express SARS-CoV-2 and porcine epidemic diarrhea virus (PEDV) fusion peptide (FP) on the cell surface, and evaluated their use as killed whole-cell vaccines. The FP sequence is highly conserved across coronaviruses; the six FP core amino acid residues, along with the four adjacent residues upstream and the three residues downstream from the core, are identical between SARS-CoV-2 and PEDV. We tested the efficacy of PEDV FP and SARS-CoV-2 FP vaccines in a PEDV challenge pig model. We demonstrated that both vaccines induced potent anamnestic responses upon virus challenge, potentiated interferon-γ responses, reduced viral RNA loads in jejunum tissue, and provided significant protection against clinical disease. However, neither vaccines elicited sterilizing immunity. Since SARS-CoV-2 FP and PEDV FP vaccines provided similar clinical protection, the coronavirus FP could be a target for a broadly protective vaccine using any platform. Importantly, the genome-reduced bacterial surface-expressed vaccine platform, when using a vaccine-appropriate bacterial vector, has potential utility as an inexpensive, readily manufactured, and rapid vaccine platform for other pathogens. |
| 巻・号 | 118(18) |
| 公開日 | 2021-5-4 |
| DOI | 10.1073/pnas.2025622118 |
| PII | 2025622118 |
| PMID | 33858942 |
| PMC | PMC8106328 |
| MeSH | Animals Antibodies, Viral / blood COVID-19 / prevention & control* COVID-19 Vaccines / immunology* Disease Models, Animal Escherichia coli / genetics Genome, Bacterial Interferon-gamma / blood Porcine epidemic diarrhea virus / immunology* RNA, Viral / analysis SARS-CoV-2 / immunology* Swine Vaccines, Inactivated / immunology Vaccines, Synthetic / immunology Viral Fusion Proteins / immunology* Viral Vaccines / immunology* |
| IF | 9.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 115 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 原核生物(大腸菌) | MG1655 ME5000 ME5010 ME5119 ME5125 |