A SARS-CoV-2 oral vaccine development strategy based on the attenuated Salmonella type III secretion system.
J Appl Microbiol
; 133(4): 2484-2500, 2022 Oct.
Article
in English
| MEDLINE | ID: covidwho-1937944
ABSTRACT
AIMS:
This study aimed to provide a safe, stable and efficient SARS-CoV-2 oral vaccine development strategy based on the type III secretion system of attenuated Salmonella and a reference for the development of a SARS-CoV-2 vaccine. METHODS ANDRESULTS:
The attenuated Salmonella mutant ΔhtrA-VNP was used as a vector to secrete the antigen SARS-CoV-2 based on the type III secretion system (T3SS). The Salmonella pathogenicity island 2 (SPI-2)-encoded T3SS promoter (sifB) was screened to express heterologous antigens (RBD, NTD, S2), and the SPI-2-encoded secretion system (sseJ) was employed to secrete this molecule (psifB-sseJ-antigen, abbreviated BJ-antigen). Both immunoblotting and fluorescence microscopy revealed effective expression and secretion of the antigen into the cytosol of macrophages in vitro. The mixture of the three strains (BJ-RBD/NTD/S2, named AisVax) elicited a marked increase in the induction of IgA or IgG S-protein Abs after oral gavage, intraperitoneal and subcutaneous administration. Flow cytometric analysis proved that AisVax caused T-cell activation, as shown by a significant increase in CD44 and CD69 expression. Significant production of IgA or IgG N-protein Abs was also detected by using psifB-sseJ-N(FL), indicating the universality of this strategy.CONCLUSIONS:
Delivery of multiple SARS-CoV-2 antigens using the type III secretion system of attenuated Salmonella ΔhtrA-VNP is a potential COVID-19 vaccine strategy. SIGNIFICANCE AND IMPACT OF THE STUDY The attenuated Salmonella strain ΔhtrA-VNP showed excellent performance as a vaccine vector. The Salmonella SPI-2-encoded T3SS showed highly efficient delivery of SARS-COV-2 antigens. Anti-loss elements integrated into the plasmid stabilized the phenotype of the vaccine strain. Mixed administration of antigen-expressing strains improved antibody induction.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Type III Secretion Systems
/
COVID-19
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
J Appl Microbiol
Journal subject:
Microbiology
Year:
2022
Document Type:
Article
Affiliation country:
Jam.15720
Similar
MEDLINE
...
LILACS
LIS