Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model

Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2025622118. doi: 10.1073/pnas.2025622118.


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.

Keywords: SARS-CoV-2; fusion peptide; genome-reduced bacteria vaccine platform; porcine epidemic diarrhea virus (PEDV); vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Antibodies, Viral
  • COVID-19 Vaccines
  • RNA, Viral
  • Vaccines, Inactivated
  • Vaccines, Synthetic
  • Viral Fusion Proteins
  • Viral Vaccines
  • Interferon-gamma