Intranasal IFNγ extends passive IgA antibody protection of mice against<i>Mycobacterium tuberculosis</i>lung infection

Reljić, Rajko; Clark, Simon; Williams, Ann; Falero-Díaz, Gustavo; Singh, Mahavir; Challacombe, Stephen; Marsh, Philip; Iványi, Juraj

doi:10.1111/j.1365-2249.2006.03012.x

Cited by 48 publications

(43 citation statements)

References 28 publications

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“…However, we and others have shown in previous studies that passive transfer of monoclonal antibodies can reduce infection with MTB in mice [9,[22][23][24][25][26][27][28], although it is unclear if active immunisation could induce similar levels of antibodies and of the same epitope specificity. Therefore, further work is required to fully characterise the role of Ab responses induced by the Nano-AH vaccine, in protection against MTB infection.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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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 forMycobacterium 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 Ag 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 i.n. immunisation of BCG-primed BALB/c mice with nanoparticles adsorbed with Ag85B-HBHA (Nano-AH 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.Keywords: Immunity r Mucosal r Nanoparticles r Tuberculosis r Vaccine Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionWith BCG considered an unsatisfactory vaccine and multi-drug resistant tuberculosis (TB) on the rise, there is an urgent need to Correspondence: Dr. Rajko Reljic e-mail: rreljic@sgul.ac.uk develop a more efficacious TB vaccine. Several new vaccine candidates are currently in clinical trials or have completed them, but none of them are able to induce sterilising immunity. Most disappointingly, a recently completed large phase-2b trial with the modified vaccinia Ankara-Ag85A-vectored vaccine in BCG-vaccinated children in South Africa failed to demonstrate any significantly added protection against TB compared with BCG alone [1]. However, many other vaccine candidates are still at the research and C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 440-449 Immunity to infection 441 development stage, and there is hope that some of them will enter the clinical trial pipeline in the near future. An alternative to either live (i.e. recombinant BCG) or the vector-based vaccines (i.e. replication deficient vaccinia virus or adenovirus) is immunisation with adjuvanted proteins, though the success of this approach has been somewhat limited because of the lack of safe and robust adjuvants. Adjuvant development has been hampered by a number of inherent difficulties, and only a few have so far been approved for human use. In particular, there is a dearth of adjuvants that are able to induce the Th1 immune responses required in TB. The only adjuvants that have been licensed for human use so ...

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Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…Antibody action could rest on its binding specificity for the Acr antigen, which is elevated in stationary phase organisms, 25 in the lungs of mice 26 and in response to NO or hypoxic stress 27,28 and notably in the highly virulent Beijing family of Mtb. 29,30 IFNg may act by amplifying the protection by IgA 17 or by stimulating Va14 þ /NK1.1 T cells. 31 The anti-IL-4 element of the CIT probably reduced the lung lavage levels of the TGFb and IL-10 deactivating Th2 cytokines which can aggravate active infection.…”

Section: Discussionmentioning

confidence: 99%

“…); TBA61, affinity purified mouse anti-Acr IgA mAb (1.5 mg/ml, antigen-binding titre 100,000), 37 mg in 25 ml per mouse i.n. 17 The time schedule of the CIT is shown schematically in Figure 1. Inoculations during the 3rd, 5th or 7th week and re-inoculation on the 9th week post-infection were given on the following days of the respective weeks: day 1, IFNg i.n.…”

Section: Combined Immunotherapy (Cit) Agents and Regimenmentioning

confidence: 99%

Prevention of the post-chemotherapy relapse of tuberculous infection by combined immunotherapy

Buccheri¹,

Reljić²,

Caccamo³

et al. 2009

Tuberculosis

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s u m m a r yWe report that a recently developed combined immunotherapy (CIT) has the capacity to prevent a spontaneous relapse of replicating Mycobacterium tuberculosis bacilli in the lungs of BALB/c, C57Bl/6 or C3H/HeJ strains of mice, following 4 weeks of non-sterilising treatment with isoniazid and rifampicin. The CIT regimen, represented by recombinant IFNg, anti-a crystalline monoclonal IgA antibody and IL-4 neutralizing polyclonal antibody, reduced the 8-week relapse of viable bacterial counts in the lungs most significantly, when CIT was inoculated during the 5th week post infection, i.e. during the 3rd week of chemotherapy. Although CIT enhanced lung granuloma area, nitric oxide, cytokine and chemokine levels in lung washings significantly, these could not be directly associated with the beneficial effect of CIT on the degree of relapse in the lungs. These results represent a proof-of-principle, that the described CIT, when combined with chemotherapy, could have potential for future development of a shorter regimen of tuberculosis treatment.

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“…Fc receptor also mediates multiple immune responses, such as cell activation, ADCC, generation of super-oxygen ion, antigen presentation, phagocytosis, and pinocytosis, playing an important role in elimination of immune complexes and regulation of immune functions of organisms. Reljic et al [13] discovered from mouse model infected with TB that anti-Mtb monoclonal antibodies, including LA M, 16 ku crystalline, and heparin-binding hemagglutinin adhesion, all function effectively in TB treatment. These antibodies indirectly protect organisms in various ways: some reduce Mtb microbial load in tissues, and some delay progression of inflammations and prolong survival time of animals.…”

Section: Antibodies Of Tb Humoral Immune Response and Their Functionsmentioning

confidence: 99%

Research progress on immune response of B lymphocytes and anti-Mycobacterium tuberculosis infection

You¹

2016

Infection International

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Multiple studies elucidated the importance of cellular immune mechanisms for protection against Mycobacterium tuberculosis. However, recent studies showed that B lymphocytes play a role that is underestimated through various interactions with cellular immune response, forming an important aspect of host defense against M. tuberculosis bacteria. Therefore, the author hereby proposes a progressive perspective for immunology of tuberculosis, i.e., cellular immunity and humoral immunity are not necessarily mutually exclusive. The present study summarizes recent studies that support the important role of B lymphocytes in terms of M. tuberculosis infection.Mycobacterium tuberculosis (Mtb) belong to Mycobacterium genus. This pathogenic species causes tuberculosis (TB). TB remains an important infectious disease nowadays. This disease can invade body organs, with pulmonary TB being the most commonly observed. Humoral immunity plays a negligible role in the defense against Mtb. However, antibodies were reported to pose effects on Mtb since the late 19th century. Humoral immunity indicates that under stimulations from antigens, as represented by B lymphocytes, i m mu noc y te s i n t he i m mu ne s y s tem of orga n i sm s differentiate and proliferate into plasma cells and synthesize various types of antibodies to generate specific immune responses with biological effects. Adoptively transferred B lymphocytes can limit deterioration of inf lammations induced by TB [1] . This condition demonstrates the important role of immunoglobulin-mediated immune regulation. The present study summarizes recent studies on humoral immunity against Mtb.

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Intranasal IFNγ extends passive IgA antibody protection of mice againstMycobacterium tuberculosislung infection

Cited by 48 publications

References 28 publications

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

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

Prevention of the post-chemotherapy relapse of tuberculous infection by combined immunotherapy

Research progress on immune response of B lymphocytes and anti-Mycobacterium tuberculosis infection

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