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Cell Biol."],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) remains a global epidemic despite the widespread use of Bacillus Calmette\u2013Gu\u00e9rin (BCG). Consequently, novel vaccines are required to facilitate a reduction in <jats:italic>Mtb<\/jats:italic> morbidity and mortality. PilVax is a peptide delivery strategy for the generation of highly specific mucosal immune responses and is based on the food\u2010grade bacterium <jats:italic>Lactococcus lactis<\/jats:italic> that is used to express selected peptides engineered within the <jats:italic>Streptococcus pyogenes<\/jats:italic> M1T1 pilus, allowing for peptide amplification, stabilization and enhanced immunogenicity. In the present study, the dominant T\u2010cell epitope from the <jats:italic>Mtb<\/jats:italic> protein Ag85B was genetically engineered into the pilus backbone subunit and expressed on the surface of <jats:italic>L. lactis<\/jats:italic>. Western blot and flow cytometry confirmed formation of pilus containing the peptide DNA sequence. B\u2010cell responses in intranasally vaccinated mice were analyzed by ELISA while T\u2010cell responses were analyzed by flow cytometry. Serum titers of peptide\u2010specific immunoglobulin (Ig) G and IgA were detected, confirming that vaccination produced antibodies against the cognate peptide. Peptide\u2010specific IgA was also detected across several mucosal sites sampled. Peptide\u2010specific CD4<jats:sup>+<\/jats:sup> T cells were detected at levels similar to those of mice immunized with BCG. PilVax immunization resulted in an unexpected increase in the numbers of CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>\u2013<\/jats:sup>CD8<jats:sup>\u2013<\/jats:sup> [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<jats:sup>+<\/jats:sup> T cells and DN T cells. This study provides insight into the antibody and peptide\u2010specific cellular immune responses generated by PilVax vaccination and demonstrates the suitability of this vaccine for conducting a protection study.<\/jats:p>","DOI":"10.1111\/imcb.12462","type":"journal-article","created":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T18:26:22Z","timestamp":1618770382000},"page":"767-781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intranasal immunization with Ag85B peptide 25 displayed on <i>Lactococcus<\/i><i>lactis<\/i> using the PilVax platform induces antigen\u2010specific B\u2010 and T\u2010cell responses"],"prefix":"10.1111","volume":"99","author":[{"given":"Samuel","family":"Blanchett","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Pathology School of Medical Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine JY","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology School of Medical Sciences The University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Biomolecular Discoveries The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sandford","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacelyn MS","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology School of Medical Sciences The University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Biomolecular Discoveries The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-7048","authenticated-orcid":false,"given":"Joanna R","family":"Kirman","sequence":"additional","affiliation":[{"name":"Maurice Wilkins Centre for Biomolecular Discoveries The University of Auckland Auckland New Zealand"},{"name":"Department of Microbiology &amp; 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