A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils
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Zaman, Mehfuz
Lepletier, Ailin
Eskandari, Sharareh
Kaden, Jacqualine
Mills, Jamie-Lee
Calcutt, Ainslie
Dooley, Jessica
Huo, Yongbao
Langshaw, Emma L
Ulett, Glen C
Batzloff, Michael R
Good, Michael F
Pandey, Manisha
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Abstract
Mucosally active subunit vaccines are an unmet clinical need due to lack of licensed immunostimulants suitable for vaccine antigens. Here, we show that intranasal administration of liposomes incorporating: the Streptococcus pyogenes peptide antigen, J8; diphtheria toxoid as a source of T cell help; and the immunostimulatory glycolipid, 3D(6-acyl) PHAD (PHAD), is able to induce long-lived humoral and cellular immunity. Mice genetically deficient in either mucosal antibodies or total antibodies are protected against S. pyogenes respiratory tract infection. Utilizing IL-17-deficient mice or depleting cellular subsets using antibodies, shows that the cellular responses encompassing, CD4+ T cells, IL-17, macrophages and neutrophils have important functions in vaccine-mediated mucosal immunity. Overall, these data demonstrate the utility of a mucosal vaccine platform to deliver multi-pronged protective responses against a highly virulent pathogen.
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Nature Communications
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14
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NHMRC
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APP1069915
APP1083548
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© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Microbiology
Biomedical and clinical sciences
Medical virology
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Ozberk, V; Zaman, M; Lepletier, A; Eskandari, S; Kaden, J; Mills, J-L; Calcutt, A; Dooley, J; Huo, Y; Langshaw, EL; Ulett, GC; Batzloff, MR; Good, MF; Pandey, M, A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils, Nature Communications, 2023, 14, pp. 5963