tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 May 4;118(18):e2025622118.
doi: 10.1073/pnas.2025622118.
Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model
Denicar Lina Nascimento Fabris Maeda[SUP] 1 2 3 [/SUP], Debin Tian[SUP] 4 5 [/SUP], Hanna Yu[SUP] 1 2 3 [/SUP], Nakul Dar[SUP] 1 2 3 [/SUP], Vignesh Rajasekaran[SUP] 1 2 3 [/SUP], Sarah Meng[SUP] 1 2 3 [/SUP], Hassan M Mahsoub[SUP] 4 5 [/SUP], Harini Sooryanarain[SUP] 4 5 [/SUP], Bo Wang[SUP] 4 5 [/SUP], C Lynn Heffron[SUP] 4 5 [/SUP], Anna Hassebroek[SUP] 4 5 [/SUP], Tanya LeRoith[SUP] 4 5 [/SUP], Xiang-Jin Meng[SUP] 6 5 [/SUP], Steven L Zeichner[SUP] 7 2 3 8 [/SUP]
Affiliations
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-? 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.
Keywords: SARS-CoV-2; fusion peptide; genome-reduced bacteria vaccine platform; porcine epidemic diarrhea virus (PEDV); vaccine.
. 2021 May 4;118(18):e2025622118.
doi: 10.1073/pnas.2025622118.
Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model
Denicar Lina Nascimento Fabris Maeda[SUP] 1 2 3 [/SUP], Debin Tian[SUP] 4 5 [/SUP], Hanna Yu[SUP] 1 2 3 [/SUP], Nakul Dar[SUP] 1 2 3 [/SUP], Vignesh Rajasekaran[SUP] 1 2 3 [/SUP], Sarah Meng[SUP] 1 2 3 [/SUP], Hassan M Mahsoub[SUP] 4 5 [/SUP], Harini Sooryanarain[SUP] 4 5 [/SUP], Bo Wang[SUP] 4 5 [/SUP], C Lynn Heffron[SUP] 4 5 [/SUP], Anna Hassebroek[SUP] 4 5 [/SUP], Tanya LeRoith[SUP] 4 5 [/SUP], Xiang-Jin Meng[SUP] 6 5 [/SUP], Steven L Zeichner[SUP] 7 2 3 8 [/SUP]
Affiliations
- PMID: 33858942
- DOI: 10.1073/pnas.2025622118
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-? 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.
Keywords: SARS-CoV-2; fusion peptide; genome-reduced bacteria vaccine platform; porcine epidemic diarrhea virus (PEDV); vaccine.