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  1. Article ; Online: Mucosal vaccination: onward and upward.

    Tsai, Catherine J Y / Loh, Jacelyn M S / Fujihashi, Kohtaro / Kiyono, Hiroshi

    Expert review of vaccines

    2023  Volume 22, Issue 1, Page(s) 885–899

    Abstract: Introduction: The unique mucosal immune system allows the generation of robust protective immune responses at the front line of pathogen encounters. The needle-free delivery route and cold chain-free logistic requirements also provide additional ... ...

    Abstract Introduction: The unique mucosal immune system allows the generation of robust protective immune responses at the front line of pathogen encounters. The needle-free delivery route and cold chain-free logistic requirements also provide additional advantages in ease and economy. However, the development of mucosal vaccines faces several challenges, and only a handful of mucosal vaccines are currently licensed. These vaccines are all in the form of live attenuated or inactivated whole organisms, whereas no subunit-based mucosal vaccine is available.
    Areas covered: The selection of antigen, delivery vehicle, route and adjuvants for mucosal vaccination are highly important. This is particularly crucial for subunit vaccines, as they often fail to elicit strong immune responses. Emerging research is providing new insights into the biological and immunological uniqueness of mucosal tissues. However, many aspects of the mucosal immunology still await to be investigated.
    Expert opinion: This article provides an overview of the current understanding of mucosal vaccination and discusses the remaining knowledge gaps. We emphasize that because of the potential benefits mucosal vaccines can bring from the biomedical, social and economic standpoints, the unmet goal to achieve mucosal vaccine success is worth the effort.
    MeSH term(s) Humans ; Vaccination ; Mucous Membrane ; Vaccines ; Immunity ; Adjuvants, Immunologic ; Immunity, Mucosal
    Chemical Substances Vaccines ; Adjuvants, Immunologic
    Language English
    Publishing date 2023-10-17
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2181284-6
    ISSN 1744-8395 ; 1476-0584
    ISSN (online) 1744-8395
    ISSN 1476-0584
    DOI 10.1080/14760584.2023.2268724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pilus proteins from Streptococcus pyogenes stimulate innate immune responses through Toll-like receptor 2.

    Takahashi, Risa / Radcliff, Fiona J / Proft, Thomas / Tsai, Catherine J-Y

    Immunology and cell biology

    2022  Volume 100, Issue 3, Page(s) 174–185

    Abstract: The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS ... ...

    Abstract The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS virulence, the pilus has become an attractive target for vaccine development. While current research mainly focuses on pilus function and its potential as a vaccine component, there is a lack of knowledge on how the host immune system recognizes and responds to this abundant surface structure. Here we show that both assembled GAS pili and individual pilus proteins induce a potent release of the proinflammatory cytokines tumor necrosis factor and interleukin-8. We further show that the surface-exposed backbone pilin and ancillary pilin 1 subunits are Toll-like receptor 2 (TLR2) agonists. Using reporter cell lines coexpressing human TLR2 in combination with either TLR1 or TLR6, we determined that activation was mediated by the TLR2/TLR6 heterodimer. Finally, we used solid-phase and flow cytometry binding assays to illustrate a direct interaction between the pilus subunits and TLR2. These results provide further support for the suitability of the pilus as a vaccine component and opens potential avenues for using GAS pili as an adjuvant or immune-modulation agent.
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Fimbriae Proteins/metabolism ; Humans ; Immunity, Innate ; Streptococcus pyogenes/metabolism ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 6/metabolism
    Chemical Substances Bacterial Proteins ; Toll-Like Receptor 2 ; Toll-Like Receptor 6 ; Fimbriae Proteins (147680-16-8)
    Language English
    Publishing date 2022-02-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Publisher Correction: Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses.

    Loh, Jacelyn M S / Lorenz, Natalie / Tsai, Catherine J-Y / Khemlani, Adrina Hema J / Proft, Thomas

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 6975

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
    Language English
    Publishing date 2019-05-01
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-43123-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses.

    Loh, Jacelyn M S / Lorenz, Natalie / Tsai, Catherine J-Y / Khemlani, Adrina Hema J / Proft, Thomas

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 7174

    Abstract: The human pathogen Group A Streptococcus (GAS) produces pili that are involved in adhesion and colonisation of the host. These surface-exposed pili are immunogenic and therefore represent an attractive target for vaccine development. The pilus is encoded ...

    Abstract The human pathogen Group A Streptococcus (GAS) produces pili that are involved in adhesion and colonisation of the host. These surface-exposed pili are immunogenic and therefore represent an attractive target for vaccine development. The pilus is encoded in the genomic region known as the fibronectin-collagen-T-antigen (FCT)-region, of which at least nine different types have been identified. In this study we investigate expressing two of the most common FCT-types (FCT-3 and FCT-4) in the food-grade bacteria Lactococcus lactis for use as a mucosal vaccine. We show that mucosally delivered L. lactis expressing GAS pili generates specific antibody responses in rabbits. Rabbit anti-pilus antibodies were shown to have both a neutralising effect on bacterial adhesion, and immunised rabbit antiserum was able to facilitate immune-mediated killing of bacteria via opsonophagocytosis. Furthermore, intranasal immunisation of mice improved clearance rates of GAS after nasopharyngeal challenge. These results demonstrate the potential for a novel, pilus-based vaccine to protect against GAS infections.
    MeSH term(s) Animals ; Antigens, Bacterial ; Fibronectins ; Fimbriae Proteins/genetics ; Fimbriae Proteins/immunology ; Fimbriae, Bacterial/genetics ; Fimbriae, Bacterial/immunology ; Lactococcus lactis/genetics ; Lactococcus lactis/immunology ; Mice ; Rabbits ; Streptococcal Infections ; Streptococcal Vaccines/immunology ; Streptococcal Vaccines/pharmacology ; Streptococcus pyogenes/genetics ; Streptococcus pyogenes/immunology ; Vaccination ; Vaccines, Synthetic/immunology
    Chemical Substances Antigens, Bacterial ; Fibronectins ; Streptococcal Vaccines ; Vaccines, Synthetic ; Fimbriae Proteins (147680-16-8)
    Language English
    Publishing date 2017-08-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-07602-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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