Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Generation of E. coli Nissle Expressing SARS-CoV-2 Spike Protein on Cell Membrane as Immunogen
2.2. Immunofluorescent Analysis of Spike Protein Expression on the Bacterial Surface
2.3. Western Blot Analysis of Spike Protein Expression
2.4. Animals, Immunization Protocol, and Sample Collection
2.5. Assessment of Safety Profile and Adverse Effects
2.6. ELISA for Specific Anti-SARS-CoV-2 S Antibodies Detection
2.7. Relative Avidity Index for Anti-SARS-CoV-2 SP IgA and IgG
2.8. Immunofluorescence Analysis
2.9. Histopathological Analysis
2.10. Enzyme-Linked Immunosorbent Assay for LPS
2.11. Statistical Analysis
3. Results
3.1. Expression of SARS-CoV-2 Spike Protein by Engineered E. coli Nissle
3.2. EcN-pAIDA1-SP Is Capable of Expressing and Delivering the SARS-CoV-2 SP to the Intestinal Site
3.3. Engineered EcN-pAIDA1-SP Elicits a Time-Dependent Increase in Circulating Anti-SARS-CoV-2 SP IgGs
3.4. Engineered EcN-pAIDA1-SP Induces a Specific IgA-Mediated Mucosal Immune Response at Gastrointestinal and Pulmonary Interfaces
3.5. Engineered EcN-pAIDA1-SP Increases the Dendritic Cell Activity, Increases Plasma Cell Numbers in Both Colon and Spleen
3.6. Anti-SARS-CoV-2 SP IgG and IgA Exhibit a High Relative Avidity Index (RAI) for SP
3.7. EcN-pAIDA1-SP Immunization Did Not Induce Side Effects or Affect Mice Survival
4. Discussion
5. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sarnelli, G.; Del Re, A.; Pesce, M.; Lu, J.; Esposito, G.; Sanseverino, W.; Corpetti, C.; Basili Franzin, S.; Seguella, L.; Palenca, I.; et al. Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice. Biomolecules 2023, 13, 569. https://doi.org/10.3390/biom13030569
Sarnelli G, Del Re A, Pesce M, Lu J, Esposito G, Sanseverino W, Corpetti C, Basili Franzin S, Seguella L, Palenca I, et al. Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice. Biomolecules. 2023; 13(3):569. https://doi.org/10.3390/biom13030569
Chicago/Turabian StyleSarnelli, Giovanni, Alessandro Del Re, Marcella Pesce, Jie Lu, Giovanni Esposito, Walter Sanseverino, Chiara Corpetti, Silvia Basili Franzin, Luisa Seguella, Irene Palenca, and et al. 2023. "Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice" Biomolecules 13, no. 3: 569. https://doi.org/10.3390/biom13030569