Schistosoma mansoni rSm29 Antigen Induces a Regulatory Phenotype on Dendritic Cells and Lymphocytes From Patients With Cutaneous Leishmaniasis

Lopes, Diego Mota; Oliveira, Sérgio C.; Page, Brady; Carvalho, Lucas P.; Carvalho, Edgar M.; Cardoso, Luciana Santos

doi:10.3389/fimmu.2018.03122

Cited by 13 publications

(16 citation statements)

References 47 publications

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“…loop. 44,45 The main structural differences of the liganded and unliganded state are located in the CDR-H3 loop and show a Cα-RMSD of 2.3 Å. The CDR-H3 loop of this antibody contains only five amino acid residues; however, the clustering dendrogam in Figure 8 clearly shows that the CDR-H3 loop shows numerous transitions during the simulations, which underlines the relative high flexibility in solution.…”

Section: Ferrochelatase Fvmentioning

confidence: 91%

“…We followed a protocol that we developed in a previous study. 44 All starting structures for simulations were prepared in MOE (Molecular Operating Environment, Chemical Computing Group, version 2018.01) using the Protonate3D tool. 49,50 The C-termini of the antibodies were capped with N-methylamine (NME).…”

Section: Combined Simulation and Analysis Protocolmentioning

confidence: 99%

“…As the Ferrochelatase antibody was analyzed previously in a different context with a distance cutoff criterion of 1.0 Å, these data were reused. 44 The cluster representatives for the systems were equilibrated and simulated for 100 ns using the AMBER16 51 simulation package.…”

Section: Metadynamics Simulationsmentioning

confidence: 99%

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CDR-H3 loop ensemble in solution – conformational selection upon antibody binding

Fernández‐Quintero

Kraml

Georges

et al. 2019

mAbs

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We analyzed pairs of protein-binding, peptide-binding and hapten-binding antibodies crystallized as complex and in the absence of the antigen with and without conformational differences upon binding in the complementarity-determining region (CDR)-H3 loop. Here, we introduce a molecular dynamicsbased approach to capture a diverse conformational ensemble of the CDR-H3 loop in solution. The results clearly indicate that the inherently flexible CDR-H3 loop indeed needs to be characterized as a conformational ensemble. The conformational changes of the CDR-H3 loop in all antibodies investigated follow the paradigm of conformation selection, because we observe the experimentally determined binding competent conformation without the presence of the antigen within the ensemble of pre-existing conformational states in solution before binding. We also demonstrate for several examples that the conformation observed in the antibody crystal structure without antigen present is actually selected to bind the carboxyterminal tail region of the antigen-binding fragment (Fab). Thus, special care must be taken when characterizing antibody CDR-H3 loops by Fab X-ray structures, and the possibility that pre-existing conformations are present should always be considered.

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Section: Ferrochelatase Fvmentioning

confidence: 91%

Section: Combined Simulation and Analysis Protocolmentioning

confidence: 99%

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CDR-H3 loop ensemble in solution – conformational selection upon antibody binding

Fernández‐Quintero

Kraml

Georges

et al. 2019

mAbs

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“…Recent studies, nonetheless, show that, in some cases, mature DC could also display the characteristic of tolerance. For instance, stimulation by recombinant soluble Schistosoma mansoni egg antigen (rSm29) could induce mono-DC with high expression of MHC-II and costimulatory molecules while rSm29 could increase IL-10 level and decrease levels of IL-12p40 and interferon-gamma (IFN-γ) in cultured mono-DC, which results in a great therapeutic efficacy on cutaneous leishmaniasis ( 32 ).…”

Section: The Characteristics and Biomarkers Of Tol-dcmentioning

confidence: 99%

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

et al. 2020

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Over a half century, organ transplantation has become an effective method for the treatment of end-stage visceral diseases. Although the application of immunosuppressants (IS) minimizes the rate of allograft rejection, the common use of IS bring many adverse effects to transplant patients. Moreover, true transplant tolerance is very rare in clinical practice. Dendritic cells (DCs) are thought to be the most potent antigen-presenting cells, which makes a bridge between innate and adaptive immunity. Among their subsets, a small portion of DCs with immunoregulatory function was known as tolerogenic DC (Tol-DC). Previous reports demonstrated the ability of adoptively transferred Tol-DC to approach transplant tolerance in animal models. In this study, we summarized the properties, ex vivo generation, metabolism, and clinical attempts of Tol-DC. Tol-DC is expected to become a substitute for IS to enable patients to achieve immune tolerance in the future.

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“…93 Taken together with data from other studies, the strong protective capacity of rVSV-MARV seems to be primarily mediated by a strong humoral immune response. 24,89,92,94 Combination of rVSV-vectored filovirus vaccines While the largest EVD outbreaks to date have been caused by EBOV, EVD outbreaks caused by other ebolavirus species have also been described, and MARV and EBOV outbreaks occur in overlapping geographic regions. Cross-protection of VSV-EBOV and -MARV against heterologous strains has been demonstrated as outlined above; 50,89 however, limited or no cross-protection might exist between the more distantly related species and genera.…”

Section: Marburg Virusmentioning

confidence: 99%

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi

Dahlke

Addo

2019

Human Vaccines & Immunotherapeutics

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The devastating Ebola virus (EBOV) outbreak in West Africa in 2013-2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens. ARTICLE HISTORY

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Schistosoma mansoni rSm29 Antigen Induces a Regulatory Phenotype on Dendritic Cells and Lymphocytes From Patients With Cutaneous Leishmaniasis

Cited by 13 publications

References 47 publications

CDR-H3 loop ensemble in solution – conformational selection upon antibody binding

CDR-H3 loop ensemble in solution – conformational selection upon antibody binding

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

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