Significance We report a vaccine platform to express vaccine antigens on the surface of genome-reduced bacteria to enhance vaccine immunogenicity. We demonstrate the utility of this vaccine platform by expressing the highly conserved fusion peptide (FP) of SARS-CoV-2 and porcine epidemic diarrhea virus on the surface of Escherichia coli to produce killed whole-cell bacterial vaccines. The vaccine primes a potent anamnestic response, potentiates interferon-γ responses, and provides significant protection in pigs against disease following virus challenge. The FP could be a target for a broadly protective coronavirus vaccine since a betacoronavirus SARS-CoV-2 FP vaccine provided cross-protection against alphacoronavirus porcine epidemic diarrhea virus. When using a vaccine-appropriate bacteria vector, this inexpensive vaccine platform offers the potential for use in developing countries. 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.
【저자키워드】 SARS-CoV-2, Vaccine, fusion peptide, genome-reduced bacteria vaccine platform, porcine epidemic diarrhea virus (PEDV), 【초록키워드】 COVID-19, coronavirus disease, Coronavirus disease 2019, Efficacy, coronavirus, pandemic, cross-protection, Immunity, Vaccines, interferon, peptide, immune system, diarrhea, virus, Betacoronavirus, sterilizing immunity, target, Pathogens, Bacteria, coronavirus vaccine, vaccine platform, utility, viral RNA load, disease, platform, anamnestic response, Protective, Bacterial, Amino acid, Interaction, Escherichia coli, vaccine immunogenicity, epidemic diarrhea, Transport, interferon-γ, tissue, cell surface, principle, residue, sequence, PEDV, amino acid residues, PIGS, proof, core, Express, clinical disease, vaccine antigen, upstream, offer, downstream, expression vector, responses, Cell, ENhance, highly conserved fusion peptide, tested, conserved, evaluated, provided, reduced, provide, demonstrated, expressing, elicited, Significance, 【제목키워드】 coronavirus, disease, whole-genome, PROTECT,