Mucosal delivery of antigen-coated nanoparticles to lungs confers protective immunity against tuberculosis infection in mice

Infection and Immunity Research Centre, St George's University of London, UK
European Journal of Immunology (Impact Factor: 4.03). 02/2014; 44(2). DOI: 10.1002/eji.201343887
Source: PubMed


Mucosal boosting of BCG-immunised individuals with a subunit tuberculosis (TB) vaccine would be highly desirable, considering that the lungs are the principal port of entry for Mycobacterium tuberculosis (MTB) and the site of the primary infection and reactivation. However, the main roadblock for subunit TB vaccine development is the lack of suitable adjuvants that could induce robust local and systemic immune responses. Here, we describe a novel vaccine delivery system that was designed to mimic, in part, the MTB pathogen itself. The surface of yellow carnauba wax nanoparticles was coated with the highly immunogenic Ag85B antigen of MTB and they were directed to the alveolar epithelial surfaces by the incorporation of the heparin-binding hemagglutinin adhesion (HBHA) protein. Our results showed that the intranasal immunisation of BCG-primed BALB/c mice with nanoparticles adsorbed with Ag85B-HBHA (NanoAH vaccine) induced robust humoral and cellular immune responses and IFN-γ production, and multifunctional CD4(+) T cells expressing IFN-γ, IL-2 and TNF-α. Mice challenged with H37Rv MTB had a significantly reduced bacterial load in their lungs when compared with controls immunised with BCG alone. We therefore conclude that this immunisation approach is an effective means of boosting the BCG-induced anti-TB immunity. This article is protected by copyright. All rights reserved.

Download full-text


Available from: Laura Sibley, Mar 30, 2014
60 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza A virus strains. We analyzed the impact of influenza A virus and mycobacterial respiratory coinfection on the development of CD8 T cell responses to each pathogen. Coinfected mice exhibited reduced frequency and numbers of CD8 T cells specific to Mycobacterium bovis bacille Calmette-Guérin (BCG) in the lungs, and the IFN-γ CD8 T cell response to BCG-encoded OVA was decreased in the lungs of coinfected mice, when compared with mice infected with BCG alone. Moreover, after 2 wk of infection, mice coinfected with both pathogens showed a significant increase in the number of mycobacteria present in the lung compared with mice infected with BCG only. Following adoptive transfer into coinfected mice, transgenic CD8 T cells specific for OVA257-264 failed to proliferate as extensively in the mediastinal lymph nodes as in mice infected only with BCG-OVA. Also noted was a reduction in the proliferation of BCG-specific CD4 transgenic T cells in mice coinfected with influenza compared with mice infected with BCG alone. Furthermore, phenotypic analysis of CD11c(+) dendritic cells from mediastinal lymph nodes of the infected mice showed that coinfection was associated with decreased surface expression of MHC class II and class I. Thus, concurrent pulmonary infection with influenza A virus is associated with decreased MHC expression on dendritic cells, reduced activation of BCG-specific CD4 and CD8 T cells, and impaired clearance of mycobacteria.
    The Journal of Immunology 05/2013; 191(1). DOI:10.4049/jimmunol.1202824 · 4.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Next-generation vaccines for tuberculosis should be designed to prevent the infection and to achieve sterile eradication of Mycobacterium tuberculosis. Mucosal vaccination is a needle-free vaccine strategy that provides protective immunity against pathogenic bacteria and viruses in both mucosal and systemic compartments, being a promising alternative to current tuberculosis vaccines. Micro and nanoparticles have shown great potential as delivery systems for mucosal vaccines. In this review, the immunological principles underlying mucosal vaccine development will be discussed, and the application of mucosal adjuvants and delivery systems to the enhancement of protective immune responses at mucosal surfaces will be reviewed, in particular those envisioned for oral and nasal routes of administration. An overview of the essential vaccine candidates for tuberculosis in clinical trials will be provided, with special emphasis on the potential different antigens and immunization regimens.
    Journal of Biomedical Nanotechnology 09/2014; 10(9):2295-2316. DOI:10.1166/jbn.2014.1984 · 5.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mucosal sites serve as the main portal for the entry of pathogens and thus immunization through mucosal routes can greatly improve the immunity. Researchers are continuously exploring the vaccination strategies to engender protective mucosal immune responses. Unearthing of mucosal adjuvants, that are safe and effective, is enhancing the magnitude and quality of the protective immune response. Use of nanotechnology based polymeric nanocarrier systems which encapsulate vaccine components for protection of sensitive payload, incorporate mucosal adjuvants to maximize the immune responses and target the mucosal immune system is key strategy to improve the effectiveness of mucosal vaccines. These advances promise to accelerate the development and testing of new mucosal vaccines against many human diseases. This review focuses the need for the development of nanocarrier based mucosal vaccines with emphases on the polymeric nanoparticles, their clinical status and future perspectives. This review focuses the need and new insights for the development of nanoarchitectures governed mucosal vaccination with emphases on the various polymeric nanoparticles, their clinical status and future perspectives. Copyright © 2014. Published by Elsevier Inc.
    Biotechnology Advances 12/2014; DOI:10.1016/j.biotechadv.2014.12.004 · 9.02 Impact Factor
Show more

Similar Publications