Molecular adjuvants that modulate regulatory T cell function in vaccination: A critical appraisal

Batista-Duharte, Alexander; Téllez-Martínez, Damiana; Fuentes, Deivys Leandro Portuondo; Carlos, Iracilda Zeppone

doi:10.1016/j.phrs.2017.11.026

Cited by 23 publications

(18 citation statements)

References 171 publications

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“…Owing to the inhibition of Th17 development by IL-2, the enhancement of Th17 cell abundance was, in part, attributable to the Tregs preferential consumption of IL-2 (Pandiyan et al, 2011;Whibley et al, 2014). Tregs can differentiate into Th17 cells in the presence of IL-6 (and in the absence of exogenous TGF-b) and induce naive CD4þCD25ÀT-cell differentiation into IL-17-producing cells, (Kitani and Xu, 2008;Batista-Duharte et al, 2018b). In contrast, other studies using the same infectious agent, C. albicans, have suggested an inhibitory effect of Tregs on Th17 activity (De Luca et al, 2007).…”

Section: S Brasiliensismentioning

confidence: 99%

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

et al. 2018

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Little is known about the differences in the CD4þ T-cell response induced by Sporothrix schenckii and Sporothrix brasiliensis, the most virulent species that cause sporotrichosis. Here, the helper (Th) and regulatory T cells (Tregs) responses were evaluated comparatively in a murine model of sporotrichosis on days 7, 21 and 35 after subcutaneous infection with either S. schenckii or S. brasiliensis conidia. The fungal load was measured at the site of infection, as well as in the liver and spleen. The Th1/Th17/Tregs responses were analyzed in the spleen, while the level of IL-2, IL-4, IL-6, TNF-alpha, IFN-ɣ, IL-17A and IL-10 cytokines were measured at the local site of infection on 24 h postinfections and in sera on the indicated days. S. brasiliensis caused a longer-lasting infection in the skin and chronic systemic dissemination associated to more severe granulomatous lesions. Similar Th1/Th1-Th17/Tregs responses were induced by both S. brasiliensis and S. schenckii on 7th and 21st d.p.i but on 35 d.p.i a reduction of Th1 and Th1-Th17 cells, associated to higher values of Th17/Tregs cells was observed only in S. brasiliensis-infected mice. In summary, S. brasiliensis caused a more severe disease associated with sustained Th17/Tregs responses than S. schenckii in mice.

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Section: S Brasiliensismentioning

confidence: 99%

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

et al. 2018

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“…Moreover, one of the most interesting aspects is to achieve an adequate efficacy/toxicity balance of the vaccines and adjuvants frequently causes adverse reactions [30]. For this reason, the search for alternatives using molecular modulators seems to be a promising way [31]. Since activated DCs may be more efficient than nonspecific commercial adjuvants, we propose that SsCWP-stimulated BMDCs could represent a potential therapeutic tool for sporotrichosis management.…”

Section: Discussionmentioning

confidence: 99%

Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro

Quinello

Ferreira

Picolli

et al. 2018

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Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate  the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

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“…One of the current directions of this approach is the development of subunit vaccines that contain only the minimal microbial component necessary to stimulate long-lasting protective or therapeutic immune responses [149]. In the meantime, another direction is targeting immune regulatory networks with molecular adjuvants for improving vaccine immunogenicity with the lowest possible toxicity [150]. Several ASOs have been evaluated as adjuvants to enhance the immune response in experimental vaccines.…”

Section: Asos As Vaccine Adjuvants In Subunit Vaccinesmentioning

confidence: 99%

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

et al. 2020

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Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to their high specificity and well-known mechanism of action, there has been a growing interest in using them for improving vaccine efficacy. Several studies have shown that ASOs can improve the efficacy of vaccines either by inducing antigen modification such as enhanced expression of immunogenic molecules or by targeting certain components of the host immune system to achieve the desired immune response. However, despite their extended use, some problems such as insufficient stability and low cellular delivery have not been sufficiently resolved to achieve effective and safe ASO-based vaccines. In this review, we analyze the molecular bases and the research that has been conducted to demonstrate the potential use of ASOs in vaccines.

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Molecular adjuvants that modulate regulatory T cell function in vaccination: A critical appraisal

Cited by 23 publications

References 171 publications

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

<em>Sporothrix schenckii</em> Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile<strong> <em>In Vitro</em></strong>

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

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