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  • Self-adjuvanting modular virus-like particles for mucosal vaccination against group A streptococcus (GAS)

    Author(s)
    Rivera-Hernandez, Tania
    Hartas, Jon
    Wu, Yang
    Chuan, Yap P
    Lua, Linda HL
    Good, Michael
    Batzloff, Michael R
    Middelberg, Anton PJ
    Griffith University Author(s)
    Good, Michael F.
    Year published
    2013
    Metadata
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    Abstract
    Group A streptococcus (GAS) causes a wide range of diseases, some of them related to autoimmune diseases triggered by repeated GAS infections. Despite the fact that GAS primarily colonizes the mucosal epithelium of the pharynx, the main mechanism of action of most vaccine candidates is based on development of systemic antibodies that do not cross-react with host tissues, neglecting the induction of mucosal immunity that could potentially block disease transmission. Peptide antigens from GAS M-surface protein can confer protection against infection; however, translation of such peptides into immunogenic mucosal vaccines that ...
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    Group A streptococcus (GAS) causes a wide range of diseases, some of them related to autoimmune diseases triggered by repeated GAS infections. Despite the fact that GAS primarily colonizes the mucosal epithelium of the pharynx, the main mechanism of action of most vaccine candidates is based on development of systemic antibodies that do not cross-react with host tissues, neglecting the induction of mucosal immunity that could potentially block disease transmission. Peptide antigens from GAS M-surface protein can confer protection against infection; however, translation of such peptides into immunogenic mucosal vaccines that can be easily manufactured remains a challenge. In this work, a modular murine polyomavirus (MuPyV) virus-like particle (VLP) was engineered to display a GAS antigenic peptide, J8i. Heterologous modules containing one or two J8i antigen elements were integrated with the MuPyV VLP, and produced using microbial protein expression, standard purification techniques and in vitro VLP assembly. Both modular VLPs, when delivered intranasally to outbred mice without adjuvant, induced significant titers of J8i-specific IgG and IgA antibodies, indicating significant systemic and mucosal responses, respectively. GAS colonization in the throats of mice challenged intranasally was reduced in these immunized mice, and protection against lethal challenge was observed. This study shows that modular MuPyV VLPs prepared using microbial synthesis have potential to facilitate cost-effective vaccine delivery to remote communities through the use of mucosal immunization.
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    Journal Title
    Vaccine
    Volume
    31
    Issue
    15
    DOI
    https://doi.org/10.1016/j.vaccine.2013.02.013
    Subject
    Biological sciences
    Bacteriology
    Agricultural, veterinary and food sciences
    Biomedical and clinical sciences
    Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies)
    Publication URI
    http://hdl.handle.net/10072/55592
    Collection
    • Journal articles

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