Development of the Brazilian Anti Schistosomiasis Vaccine Based on the Recombinant Fatty Acid Binding Protein Sm14 Plus GLA-SE Adjuvant

Tendler, Míriam; Almeida, Marília Sirianni dos Santos; Simpson, Andrew

doi:10.3389/fimmu.2015.00218

Cited by 47 publications

(56 citation statements)

References 41 publications

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“…Previous studies have found that GLA-SE, formulated with the recombinant fatty acid binding protein Sm14, enhances Th-1 type responses. Production of IFN-γ was the basis of Sm-14-mediated protective immunity both in humans with schistosomiasis and animal models (40). This Sm14 antischistosome vaccine is safe and entering phase 2 trials in Brazil and Africa.…”

Section: Discussionmentioning

confidence: 99%

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

et al. 2016

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We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8(+) T cell-eliciting epitopes, a universal CD4(+) helper T lymphocyte epitope (PADRE), and a secretory signal, all arranged for optimal MHC-I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8(+) T cells that produced IFN-γ and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens must account for the immunogenicity of our adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of peptides resulting in cross presentation of CD8(+) T cell-eliciting epitopes in a vaccine that prevents toxoplasmosis

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Section: Discussionmentioning

confidence: 99%

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

et al. 2016

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“…Compartmental model simulation of schistosomiasis transmission in endemic regions has predicted that, compared with MDA‐only programs, vaccination with a partially protective vaccine combined with MDA would be advantageous in reducing the acquisition of new worms and lowering egg release from residual worms in the environment . To date, there are three schistosomiasis vaccine candidates in various phases of human clinical trials: S. haematobium glutathione S ‐transferase (Sh28GST), S. mansoni tetraspanin, a 9‐kDa surface antigen (Sm‐TSP‐2), and S. mansoni 14‐kDa fatty acid‐binding protein (Sm14) …”

Section: Introductionmentioning

confidence: 99%

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Zhang

Molehin

Rojo

et al. 2018

Annals of the New York Academy of Sciences

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Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80-based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg-induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg-load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission-blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80-specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80-based vaccine for schistosomiasis.

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“…5 Furthermore, Tendler and colleagues have demonstrated that the use of vaccines containing epitopes of the Sm14 protein could induce a level of protection similar to that observed with the recombinant protein. 8 This result indicates that the use of peptide may be a promising strategy in the development of new vaccines.…”

mentioning

confidence: 93%

Epitopes rationally selected through computational analyses induce T‐cell proliferation in mice and are recognized by serum from individuals infected with Schistosoma mansoni

Lopes

Oliveira

Coelho

et al. 2017

Biotechnology Progress

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Schistosomiasis is the second leading cause of death due to parasitic diseases in the world. Seeking an alternative for the control of disease, the World Health Organization funded the genome sequencing of the major species related to schistosomiasis to identify potential vaccines and therapeutic targets. Therefore, the aim of this work was to select T and B-cell epitopes from Schistosoma mansoni through computational analyses and evaluate the immunological potential of epitopes in vitro. Extracellular regions of membrane proteins from the Schistosoma mansoni were used to predict promiscuous epitopes with affinity to different human Major Histocompatibility Class II (MHCII) molecules by bioinformatics analysis. The three-dimensional structure of selected epitopes was constructed and used in molecular docking to verify the interaction with murine MHCII H2-IA . In this process, four epitopes were selected and synthesized to assess their ability to stimulate proliferation of CD4 T lymphocytes in mice splenocyte cultures. The results showed that Sm041370 and Sm168240 epitopes induced significant cell proliferation. Additionally, the four epitopes were used as antigens in the Indirect Enzyme-Linked Immunosorbent Assay (ELISA) to assess the recognition by serum from individuals infected with Schistosoma mansoni. Sm140560, Sm168240, and Sm041370 epitopes were recognized by infected individuals IgG antibodies. Therefore, Sm041370 and Sm168240 epitopes that stood out in in silico and in vitro analyses could be promising antigens in schistosomiasis vaccine development or diagnostic kits. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:804-814, 2017.

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Development of the Brazilian Anti Schistosomiasis Vaccine Based on the Recombinant Fatty Acid Binding Protein Sm14 Plus GLA-SE Adjuvant

Cited by 47 publications

References 41 publications

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Epitopes rationally selected through computational analyses induce T‐cell proliferation in mice and are recognized by serum from individuals infected with Schistosoma mansoni

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