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Primary intervention programs have had limited success thus far, and a licensed vaccine has yet to be developed. The pilus of GAS is known to be involved in host cell adhesion, biofilm formation and immune evasion. We have a mucosal vaccine in development that expresses the pilus of GAS on the surface of the nonpathogenic bacterium <jats:italic>Lactococcus lactis.<\/jats:italic> To expand strain coverage, we combined seven <jats:italic>L. lactis<\/jats:italic> constructs, each expressing a different GAS pilus variant, and investigated the systemic and mucosal immune responses following immunization. Mice immunized with this combination showed specific immunoglobin G and immunoglobin A responses to the GAS pilus proteins of vaccine strains, at levels comparable to mice immunized with a single construct. Cross\u2010reactivity to pilus proteins of nonvaccine strains was also evident. Furthermore, protective efficacy against a homologous strain of GAS in a murine nasopharyngeal colonization model was observed. Overall, this study provides further evidence for using pilus\u2010expressing lactic acid bacteria as a vaccine to prevent upper respiratory tract GAS infections.<\/jats:p>","DOI":"10.1111\/imcb.12643","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:53:55Z","timestamp":1679896435000},"page":"545-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding strain coverage of a group A <i>Streptococcus<\/i> pilus\u2013expressing <i>Lactococcus lactis<\/i> mucosal vaccine"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-090X","authenticated-orcid":false,"given":"Adrina Hema","family":"J\u2010Khemlani","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Private Bag 92019 Auckland New\u00a0Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devaki","family":"Pilapitiya","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Private Bag 92019 Auckland New\u00a0Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-5552","authenticated-orcid":false,"given":"Catherine Jia\u2010Yun","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Private Bag 92019 Auckland New\u00a0Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery The University of Auckland  Private Bag 92019 Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-5042","authenticated-orcid":false,"given":"Thomas","family":"Proft","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Private Bag 92019 Auckland New\u00a0Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery The University of Auckland  Private Bag 92019 Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-1215","authenticated-orcid":false,"given":"Jacelyn Mei San","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; 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