Induction of Cell-Mediated Immunity against<i>Mycobacterium tuberculosis</i>Using DNA Vaccines Encoding Cytotoxic and Helper T-Cell Epitopes of the 38-Kilodalton Protein

Fonseca, Dora P. A. J.; Benaissa-Trouw, Barry J.; Engelen, Marloes van; Kraaijeveld, Cees A.; Snippe, H.; Verheul, A. F. M.

doi:10.1128/iai.69.8.4839-4845.2001

Cited by 39 publications

(30 citation statements)

References 40 publications

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“…Huygen et al showed that DNA vaccines based on Ag85A reduced bacterial burdens in organs after aerosol or IV M. tuberculosis challenge by establishing a cellular immune response characterized by antigenspecific IFNγ production and CD8 + CTL activity [85]. Vaccination with plasmid DNA encoding the 38 kDa protein of M. tuberculosis also elicited antigen-specific CD8 + T cell responses [86]. Similarly, immunization of mice with DNA encoding Mtb72 fusion protein elicits a strong CD4+ and CD8+ T cell response and this vaccine prolongs the survival of guinea pigs following aerosol challenge with M. tuberculosis [87].…”

Section: Dna Vaccinationmentioning

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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Section: Dna Vaccinationmentioning

confidence: 99%

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

Behar

Woodworth

2007

Expert Review of Vaccines

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“…The six antigens used in our study were chosen based on their immune properties, which have been described elsewhere (5,7,11,18,44,52). To compare their levels of recognition by the immune system during experimental mycobacterial infection, we measured IFN-␥ and IL-10 secretion by splenocytes of BCG vaccinated mice after being stimulated with each antigen.…”

Section: Antigen Recognition During Experimental Bcg Infectionmentioning

confidence: 99%

“…All antigens were selected for their reported ability to be recognized by the im-mune system or to induce Th1-type immunity (5,7,11,18,44,52). MPL and TDM that enhance Th1-type immunity (24,45) were used as adjuvants in the presence or absence of IFN-␥.…”

mentioning

confidence: 99%

Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants forMycobacterium tuberculosisMultivalent Acellular Vaccine

2005

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In this study, we examined the immunogenicity and protective efficacy of six immunodominant Mycobacterium tuberculosis recombinant antigens (85B, 38kDa, ESAT-6, CFP21, Mtb8.4, and 16kDa) in a multivalent vaccine preparation (6Ag). Gamma interferon (IFN-␥) and monophosphoryl lipid A-trehalose dicorynomycolate (Ribi) adjuvant systems were used separately or in combination for immunization with the recombinant antigens. Our results demonstrate that immunization of mice with Ribi emulsified antigens in the presence of IFN-␥ (Ribi؉6Ag؉IFN-␥) resulted after challenge with a virulent M. tuberculosis strain in a significant reduction in the CFU counts that was comparable to that achieved with the BCG vaccine (ϳ0.9-log protection). Antigen-specific immunoglobulin G (IgG) titers in the Ribi؉6Ag؉IFN-␥-immunized mice were lower than in mice immunized with Ribi؉6Ag and were oriented toward a Th1-type response, as confirmed by elevated IgG2a levels. In addition, splenocyte proliferation, IFN-␥ secretion, and NO production were significantly higher in splenocytes derived from Ribi؉6Ag؉IFN-␥-immunized mice, whereas IL-10 secretion was decreased. These findings confirm the induction of a strong cellular immunity in the vaccinated mice that correlates well with their enhanced resistance to M. tuberculosis. The adjuvant effect of IFN-␥ was dose dependent. A dose of 5 g of IFN-␥ per mouse per immunization gave optimal protection, whereas lower or higher amounts (0.5 or 50 g/ mouse) of IFN-␥ failed to enhance protection.

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“…The serologic reactivity of this Ag has a stronger association with latent infection or recent exposure to M. tuberculosis than with active disease (5,41), and therefore the 38-kDa Ag is included in all serodiagnostic assays for active tuberculosis (TB). In addition, DNA vaccines encoding cytotoxic T lymphocyte and T helper (Th1) cell epitopes of the 38-kDa lipoglycoprotein were found to elicit strong CD8 ϩ cytotoxic T lymphocyte and Th1 responses (high gamma interferon and low interleukin 4 [IL-4]) (15). Although the 38-kDa Ag has been widely used for cellular and humoral studies for TB research, little is known about the signaling mechanisms involved in the 38-kDa Ag-induced immune responses.…”

mentioning

confidence: 99%

“…Among the various protein antigens (Ags) of M. tuberculosis, the 38-kDa phosphate transport protein (PstS-1) Ag is actively secreted in mycobacterial cultures (8,21). This protein induces a strong immune response to M. tuberculosis or Mycobacterium bovis and elicits a protective immunity in animals (3,20) and humans (15,21,45). The serologic reactivity of this Ag has a stronger association with latent infection or recent exposure to M. tuberculosis than with active disease (5,41), and therefore the 38-kDa Ag is included in all serodiagnostic assays for active tuberculosis (TB).…”

mentioning

confidence: 99%

The Mycobacterial 38-Kilodalton Glycolipoprotein Antigen Activates the Mitogen-Activated Protein Kinase Pathway and Release of Proinflammatory Cytokines through Toll-Like Receptors 2 and 4 in Human Monocytes

Jung¹,

Yang²,

Lee³

et al. 2006

Infect Immun

140

119

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Although the 38-kDa glycolipoprotein of Mycobacterium tuberculosis H37Rv is known to evoke prominent cellular and humoral immune responses in human tuberculosis (TB), little information is known about intracellular regulatory mechanisms involved in 38-kDa antigen (Ag)-induced host responses. In this study, we found that purified 38-kDa glycolipoprotein activates mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2 [ERK1/2] and p38) and induces tumor necrosis factor alpha (TNF-␣) and interleukin 6 (IL-6) in human monocytes. When the 38-kDa Ag was applied to monocytes from TB patients and healthy controls, the activation of ERK1/2 and p38 MAPK and the subsequent cytokine secretion were greater in the monocytes from the active pulmonary TB patients than in monocytes from the healthy controls. Additionally, neutralizing antibodies for Toll-like receptor 2 (TLR2) or TLR4 significantly reduced the ERK1/2 and p38 activation induced by the 38-kDa protein when the antibodies were applied to HEK293 cells overexpressing TLR2 or TLR4 as well as human primary monocytes. Furthermore, the inhibition of TLR2 significantly, and that of TLR4 partially, decreased the 38-kDa Ag-induced secretion of TNF-␣ and IL-6 in human monocytes. The intact protein moieties of the 38-kDa protein were responsible for biologic activities by this Ag. These data collectively demonstrate that the 38-kDa glycolipoprotein, acting through both TLR2 and TLR4, induces the activation of the ERK1/2 and p38 MAPK pathways, which in turn play an essential role in TNF-␣ and IL-6 expression during mycobacterial infection.

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Induction of Cell-Mediated Immunity againstMycobacterium tuberculosisUsing DNA Vaccines Encoding Cytotoxic and Helper T-Cell Epitopes of the 38-Kilodalton Protein

Cited by 39 publications

References 40 publications

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

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

Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants forMycobacterium tuberculosisMultivalent Acellular Vaccine

The Mycobacterial 38-Kilodalton Glycolipoprotein Antigen Activates the Mitogen-Activated Protein Kinase Pathway and Release of Proinflammatory Cytokines through Toll-Like Receptors 2 and 4 in Human Monocytes

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Induction of Cell-Mediated Immunity againstMycobacterium tuberculosisUsing DNA Vaccines Encoding Cytotoxic and Helper T-Cell Epitopes of the 38-Kilodalton Protein

Cited by 39 publications

References 40 publications

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

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

Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants forMycobacterium tuberculosisMultivalent Acellular Vaccine

The Mycobacterial 38-Kilodalton Glycolipoprotein Antigen Activates the Mitogen-Activated Protein Kinase Pathway and Release of Proinflammatory Cytokines through Toll-Like Receptors 2 and 4 in Human Monocytes

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

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