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Intranasal immunisation with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses.

Blanchett, S; Tsai, CJ; Sandford, S; Loh, JM; Huang, L; Kirman, JR; Proft, T; (2021) Intranasal immunisation with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses. Immunology & Cell Biology , 99 (7) pp. 767-781. 10.1111/imcb.12462. Green open access

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Abstract

Mycobacterium tuberculosis (Mtb) remains a global epidemic despite the widespread use of BCG. Consequently, novel vaccines are required to facilitate a reduction in Mtb morbidity and mortality. PilVax is a peptide delivery strategy for the generation of highly specific mucosal immune responses and is based on the food-grade bacterium Lactococcus lactis that is used to express selected peptides engineered within the Streptococcus pyogenes M1T1 pilus, allowing for peptide amplification, stabilisation, and enhanced immunogenicity. In the present study, the dominant T cell epitope from the Mtb protein Ag85B was genetically engineered into the pilus backbone subunit and expressed on the surface of L. lactis. Western blot and flow cytometry confirmed formation of pilus containing the peptide DNA sequence. B cell responses in intranasally vaccinated mice were analysed by ELISA while T cell responses were analysed by flow cytometry. Serum titres of peptide specific IgG and IgA were detected, confirming vaccination produced antibodies against the cognate peptide. Peptide-specific IgA was also detected across several mucosal sites sampled. Peptide-specific CD4+ T cells were detected at levels similar to those of mice immunised with BCG. PilVax immunisation resulted in an unexpected increase in the numbers of CD3+ CD4- CD8- (double negative, DN) T cells in the lungs of vaccinated mice. Analysis of cytokine production following stimulation with the cognate peptide showed the major cytokine producing cells to be CD4+ T cells and DN T cells. This study provides insight into the antibody and peptide specific cellular immune responses generated by PilVax vaccination and demonstrates the suitability of this vaccine for conducting a protection study.

Type: Article
Title: Intranasal immunisation with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/imcb.12462
Publisher version: https://doi.org/10.1111/imcb.12462
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Mycobacterium tuberculosis, PilVax, TB, peptide, vaccine
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10127028
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