Intranasal administration of Escherichia coli Nissle expressing the spike protein of SARS-CoV-2 induces long-term immunization and prevents spike protein-mediated lung injury in mice.

Publication date: Mar 21, 2024

While current anti-Spike protein (SP) vaccines have been pivotal in managing the pandemic, their limitations in delivery, storage, and the inability to provide mucosal immunization (preventing infections) highlight the ongoing necessity for research and innovation. To tackle these constraints, our research group developed a bacterial-based vaccine using a non-pathogenic E. coli Nissle 1917 (EcN) strain genetically modified to express the SARS-CoV-2 spike protein on its surface (EcN-pAIDA1-SP). We intranasally delivered the EcN-pAIDA1-SP in two doses and checked specific IgG/IgA production as well as the key immune mediators involved in the process. Moreover, following the initial and booster vaccine doses, we exposed both immunized and non-immunized mice to intranasal delivery of SARS-CoV-2 SP to assess the effectiveness of EcN-pAIDA1-SP in protecting lung tissue from the inflammation damage. We observed detectable levels of anti-SARS-CoV-2 spike IgG in serum samples and IgA in bronchoalveolar lavage fluid two weeks after the initial treatment, with peak concentrations in the respective samples on the 35th day. Moreover, immunoglobulins displayed a progressively enhanced avidity index, suggesting a selective binding to the spike protein. Finally, the pre-immunized group displayed a decrease in proinflammatory markers (TLR4, NLRP3, ILs) following SP challenge, compared to the non-immunized groups, along with better preservation of tissue morphology. Our probiotic-based technology provides an effective immunobiotic tool to protect individuals against disease and control infection spread.

Concepts Keywords
Mice COVID-19
Mucosal Engineered probiotics
Pharmacother IgA
Tlr4 Intranasal vaccine
Vaccine Mice lung injury
NLRP3
Spike protein

Semantics

Type Source Name
disease VO immunization
disease MESH lung injury
disease VO storage
disease MESH infections
disease VO vaccine
disease IDO production
disease IDO process
disease VO immunized
disease VO effectiveness
disease MESH inflammation
drug DRUGBANK Tropicamide
disease VO effective
disease IDO infection
disease MESH COVID-19

Original Article

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