What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery?

Campos-Neto, Antônio

doi:10.1590/s0100-879x2005000700001

Cited by 52 publications

(44 citation statements)

References 36 publications

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“…Several candidate vaccine molecules have already been evaluated in the mice model for leishmaniasis (8 -14). Treatment and vaccination that control the disease in susceptible mice invariably promote Th1 responses over Th2 responses (15)(16)(17)(18). However, this may or may not hold true for other models of leishmaniasis.…”

Section: Ubiquitin Conjugation Of Open Reading Frame F Dna Vaccine Lementioning

confidence: 99%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in ∼15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-γ-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-γ and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-γ and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.

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Section: Ubiquitin Conjugation Of Open Reading Frame F Dna Vaccine Lementioning

confidence: 99%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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“…However, other studies suggest that this association is not consistently observed [17,18,19]. The induction of polarized T cell responses, and their association with infection-induced pathology or disease-protective mechanisms has led to the development of novel vaccines and immunotherapeutics [20,21].…”

Section: Discusssionmentioning

confidence: 99%

“…The concept of Th1/Th2 immune response involvement in disease pathology has recently been re-evaluated in the context of vaccine development and immunologic intervention [20,21]. In Leishmaniasis, Th1 responses are protective and th2 response are disease promoting, which is opposite to the P. gingivalis, paradigm.…”

Section: Discusssionmentioning

confidence: 99%

“…The novel hypothesis that emerges from this work is that subverting the infectious agent's ability to elicit the disease promoting phenotype can be an efficient strategy in vaccine development against microbial pathogens [20,21]. In the context of the present work, a successful immunotherapeutic candidate to halt the inflammation mediated by P. gingivalis will be a protein that during infection induces a potent Th1 response (disease promoter), when used in a vaccination formulation that induces a potent and antigen specific Th2 response.…”

Section: Discusssionmentioning

confidence: 99%

See 1 more Smart Citation

Th1 biased response to a novel Porphyromonas gingivalis protein aggravates bone resorption caused by this oral pathogen

Leshem

Kashino²,

Gonçalves

et al. 2008

Microbes and Infection

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In previous studies we showed that biasing the immune response to Porphyromonas gingivalis antigens to the Th1 phenotype increases inflammatory bone resorption caused by this organism. Using a T cell screening strategy we identified eight P. gingivalis genes coding for proteins that appear to be involved in T-helper cell responses. In the present study we characterized the protein, encoded by PG_1841 gene and evaluated its relevance in the in bone resorption caused by P. gingivalis because subcutaneous infection of mice with this organism resulted in the induction of Th1 biased response to the recombinant PG1841 antigen molecule. Using an immunization regime that strongly biases toward the Th1 phenotype followed by challenge with P. gingivalis in dental pulp tissue, we demonstrate that mice pre-immunized with rPG1841 developed severe bone loss compared with control immunized mice. Pre-immunization of mice with the antigen using a Th2 biasing regime resulted in no exacerbation of the disease.These results support the notion that selected antigens of P. gingivalis are involved in a biased Th1 host response that leads to the severe bone loss caused by this oral pathogen.

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“…So far the leishmanin (Montenegro) skin test is the most informative and practical immunological surrogate marker used in clinical trials [21]. With a complementary rationale Campos-Neto [22] has shown that disease-associated Th2 antigens of Leishmania can be protective if a Th1 response to them is generated before infection. Moreover, the immune response to a given antigen (e.g., LACK) can be protective (Th1) or exacerbating (Th2), depending on the way the antigen is introduced [23] or on the genetic background of the mouse.…”

Section: Mechanisms Of Protective Immunitymentioning

confidence: 99%