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.
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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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