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A SARS-CoV-2 oral vaccine development strategy based on the attenuated Salmonella type III secretion system.
Wu, Leyang; Li, Lin; Yin, Xingpeng; Li, Chenyang; Xin, Wenjie; Liu, Lina; Hua, Zichun.
  • Wu L; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
  • Li L; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, Jiangsu, China.
  • Yin X; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
  • Li C; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
  • Xin W; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
  • Liu L; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
  • Hua Z; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
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 AND

RESULTS:

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.
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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

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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