| 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
|
| リソース情報 |
| 原核生物(大腸菌) |
MG1655
ME5000
ME5010
ME5119
ME5125 |
