A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils

Victoria Ozberk, Mehfuz Zaman, Ailin Lepletier, Sharareh Eskandari, Jacqualine Kaden, Jamie-Lee Mills, Ainslie Calcutt, Jessica Dooley, Yongbao Huo, Emma L. Langshaw, Glen C. Ulett, Michael R. Batzloff, Michael F. Good () and Manisha Pandey ()
Additional contact information
Victoria Ozberk: Griffith University
Mehfuz Zaman: Griffith University
Ailin Lepletier: Griffith University
Sharareh Eskandari: Griffith University
Jacqualine Kaden: Griffith University
Jamie-Lee Mills: Griffith University
Ainslie Calcutt: Griffith University
Jessica Dooley: Griffith University
Yongbao Huo: Griffith University
Emma L. Langshaw: Griffith University
Glen C. Ulett: Griffith University
Michael R. Batzloff: Griffith University
Michael F. Good: Griffith University
Manisha Pandey: Griffith University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41410-7

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