Priming but not boosting with plasmid DNA encoding mycolyl-transferase Ag85A from Mycobacterium tuberculosis increases the survival time of Mycobacterium bovis BCG vaccinated mice against low dose intravenous challenge with M. tuberculosis H37Rv

Romano, Márta; D’Souza, Sushila; Adnet, Pierre-Yves; Laali, Rachid; Jurion, Fabienne; Palfliet, Kamiel; Huygen, Kris

doi:10.1016/j.vaccine.2005.12.066

Cited by 81 publications

(70 citation statements)

References 52 publications

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“…This is consistent with the recent finding that IFN-␥ suppressed the development of mycobacteria-specific IL-17-producing CD4 ϩ T cells (49). Interestingly, priming with a DNA vaccine before BCG, which increases the protective efficacy of BCG (50), was associated with both IL-17 and IFN-␥ production in wild-type mice (48). IL-18 may be a contributing factor to the IL-12/IL-23-independent induction of IL-17 production, because it is secreted in response to mycobacterial infection and can stimulate IL-17 production (51).…”

Section: Treatment Of Il-12p40supporting

confidence: 91%

“…The peak of this response was between 2 and 4 wk postimmunization, when the frequency of Ag-specific CD4 ϩ T cells secreting IL-17 was 4-fold greater than that in wild-type mice immunized with BCG (Table I). By contrast, T cells from BCG-immunized wild-type mice failed to produce IL-17 in the presence of a strong IFN-␥ response (Table I) (48). This is consistent with the recent finding that IFN-␥ suppressed the development of mycobacteria-specific IL-17-producing CD4 ϩ T cells (49).…”

Section: Treatment Of Il-12p40supporting

confidence: 89%

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Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses

Wozniak

Ryan

Britton

2006

The Journal of Immunology

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Host control of Mycobacterium tuberculosis is dependent on the activation of CD4+ T cells secreting IFN-γ and their recruitment to the site of infection. The development of more efficient vaccines against tuberculosis requires detailed understanding of the induction and maintenance of T cell immunity. Cytokines important for the development of cell-mediated immunity include IL-12 and IL-23, which share the p40 subunit and the IL-12Rβ1 signaling chain. To explore the differential effect of IL-12 and IL-23 during M. tuberculosis infection, we used plasmids expressing IL-23 (p2AIL-23) or IL-12 (p2AIL-12) alone in dendritic cells or macrophages from IL-12p40−/− mice. In the absence of the IL-12/IL-23 axis, immunization with a DNA vaccine expressing the M. tuberculosis Ag85B induced a limited Ag-specific T cell response and no control of M. tuberculosis infection. Codelivery of p2AIL-23 or p2AIL-12 with DNA85B induced strong proliferative and IFN-γ-secreting T cell responses equivalent to those observed in wild-type mice immunized with DNA85B. This response resulted in partial protection against aerosol M. tuberculosis; however, the protective effect was less than in wild-type mice owing to the requirement for IL-12 or IL-23 for the optimal expansion of IFN-γ-secreting T cells. Interestingly, bacillus Calmette-Guérin immune T cells generated in the absence of IL-12 or IL-23 were deficient in IFN-γ production, but exhibited a robust IL-17 secretion associated with a degree of protection against pulmonary infection. Therefore, exogenous IL-23 can complement IL-12 deficiency for the initial expansion of Ag-specific T cells and is not essential for the development of potentially protective IL-17-secreting T cells.

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Section: Treatment Of Il-12p40supporting

confidence: 91%

Section: Treatment Of Il-12p40supporting

confidence: 89%

Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses

Wozniak

Ryan

Britton

2006

The Journal of Immunology

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“…In part, this is because the pulmonary pathology caused by M. tuberculosis arises not only from direct toxic effects of the bacteria, but also as a consequence of immune-mediated tissue injury. Survival studies are an important way to measure the long-term benefit of vaccination [29,30], and integrate both the beneficial effect of improved bacterial control and whether improved microbial control is at the cost of greater immune-mediated inflammation that paradoxically results in more tissue damage. In practice BCG has been the standard for comparison, regardless of the measure of protection used.…”

Section: Eliciting Cd8 + T Cells and Measuring Protectionmentioning

confidence: 99%

Next generation: tuberculosis vaccines that elicit protective CD8⁺T cells

Behar

Woodworth

2007

Expert Review of Vaccines

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SummaryTuberculosis continues to cause considerable human morbidity and mortality across the world, particularly in people coinfected with HIV. The emergence of multidrug resistance makes the medical treatment of tuberculosis even more difficult. Thus, the development of a tuberculosis vaccine is a global health priority. Here we review the data concerning the role of CD8 + T cells in immunity to tuberculosis and consider how CD8 + T cells can be elicited by vaccination. Many immunization strategies have the potential to elicit CD8 + T cells, and we critically review the data supporting a role for vaccine-induced CD8 + T cells in protective immunity. The synergy between CD4 + and CD8 + T cells suggests that a vaccine which elicits both T cell subsets has the best chance at preventing tuberculosis.

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“…However, recent data from mice and cattle show that measurement of spleen or blood IFN-g-producing CD4 1 T cells does not correlate with protection [5][6][7] and that IFN-g is necessary but not sufficient for protection against M. tuberculosis. Also in humans, although IFN-g is necessary for protection against mycobacterial pathogens, it is not a correlate of protection by itself [8,9].…”

Section: Introductionmentioning

confidence: 99%

Multifunctional CD4⁺ T cells correlate with active Mycobacterium tuberculosis infection

et al. 2010

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Th1 CD41 T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-c/IL-2/TNF-a triple expressors, IFN-c/IL-2, IFN-c/TNF-a or TNF-a/IL-2 double expressors or IFN-c, IL-2 or TNF-a single expressors) of CD4 1 T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12-to 15-fold) proportions of IL-2/IFN-c double and IFN-c single expressors as compared with the other CD4 1 T-cell subsets. Proportions of the other double or single CD4 1 T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-c, IL-2 and TNF-a profiles of M. tuberculosis-specific CD4 1 T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4 1 T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy. IntroductionInfections with Mycobacterium tuberculosis (M. tuberculosis) cause a global epidemic with almost 9 million new cases and over 1.6 million deaths per year [1,2]. Outcome of M. tuberculosis infection depends on early identification and proper treatment of individuals with active tuberculosis (TB), but the lack of accurate diagnostic techniques has contributed to the re-emergence of TB as a global health threat. More than 2 billion individuals are estimated to be latently infected with M. tuberculosis (LTBI). To date, however, Ã These authors have contributed equally to this work. There were a number of differences between TB patients and subjects with LTBI following stimulation with ESAT-6, Ag85B and the 16-kDa antigen (Fig. 2). Most notably, and in contrast with the previously reported results in chronic viral infections, we found a significantly higher proportion of 31 CD4 1 T cells simultaneously secreting IFN-g, IL-2 and TNF-a in patients with TB, as compared with LTBI subjects, upon stimulation with any of the three tested M. tuberculosis antigens (Fig. 2). Using a threshold of 0.01% to avoid systematic biases incurred by zeroing negative values (frequency values o0.01% were set to zero), we found that 31 CD4 1 T cells were detectable in very few LTBI subjects (3/18, 3/18 and 2/18 in response to Ag85B, ESAT-6 and 16 kDa, respectively), but were frequently detected in most TB patients (17/20, 18/20 and 17/20, in Eur. J. Immunol. 2010. 40: 2211-2220 Nadia Caccamo et al. 2212& 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu response to Ag85B, ESAT-6 and 16 kDa, respectively; see also Table 1 for comparison).In contrast, ...

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Priming but not boosting with plasmid DNA encoding mycolyl-transferase Ag85A from Mycobacterium tuberculosis increases the survival time of Mycobacterium bovis BCG vaccinated mice against low dose intravenous challenge with M. tuberculosis H37Rv

Cited by 81 publications

References 52 publications

Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses

Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses

Next generation: tuberculosis vaccines that elicit protective CD8⁺T cells

Multifunctional CD4⁺ T cells correlate with active Mycobacterium tuberculosis infection

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Priming but not boosting with plasmid DNA encoding mycolyl-transferase Ag85A from Mycobacterium tuberculosis increases the survival time of Mycobacterium bovis BCG vaccinated mice against low dose intravenous challenge with M. tuberculosis H37Rv

Cited by 81 publications

References 52 publications

Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses

Interleukin-23 Restores Immunity to Mycobacterium tuberculosis Infection in IL-12p40-Deficient Mice and Is Not Required for the Development of IL-17-Secreting T Cell Responses

Next generation: tuberculosis vaccines that elicit protective CD8+T cells

Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection

Contact Info

Product

Resources

About

Next generation: tuberculosis vaccines that elicit protective CD8⁺T cells

Multifunctional CD4⁺ T cells correlate with active Mycobacterium tuberculosis infection