Delving into the Latest Updates on Sm-14 with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine, Genetically engineered subunit vaccine

Synonyms

Anti-schistosomiasis vaccine, Snail fever vaccine

+ [1]

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesUrogenital DiseasesOther Diseases

Active Indication

Schistosomiasis HaematobiaSchistosomiasis MansoniVaccination+ [1]

Inactive Indication-

Originator Organization

Orygen Biotecnologia Ltda.

Active Organization

Fundação Oswaldo CruzOrygen Biotecnologia Ltda.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 1120173654

Previous clinical trials have already demonstrated the safety of the candidate vaccine in adults as well as in children, in good health or infected with schistosomiasis. Regarding the induced immune response, more than 80% of vaccinated subjects were seroconverted after three vaccine injections. The induced immune response was substantial but transient. In order to obtain a more lasting immune response, the investigator will experiment with a new vaccination schedule (2 injections 1-month interval and the 3rd injection 5 months after the first dose), versus the vaccine schedule initially used (3 injections at 1-month interval).
This trial will be the last phase 2 before testing the efficacy of the rSm14 vaccine candidate.

Start Date01 Jul 2022

Sponsor / Collaborator

Fundação Oswaldo Cruz

NCT03799510 / CompletedPhase 2IIT

Safety and Immunogenicity Evaluation of the Vaccine Candidate Sm14 Against Schistosomiasis in Senegalese School Children Healthy or Infected With S. Mansoni and/or S. Haematobium. A Comparative, Randomized, Controlled, Open-label Trial

The clinical trial phase 2b is designed to assess the safety and the specific immune response of the active ingredient (protein + adjuvant) in healthy and then in infected school children from 8 to 11 years of age with intestinal and/or urinary schistosomiasis, living in the Valley of the Senegal River, a highly endemic area for schistosomiasis.

Start Date13 Dec 2018

Sponsor / Collaborator

Fundação Oswaldo Cruz

[+1]

100 Clinical Results associated with Sm-14

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100 Translational Medicine associated with Sm-14

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100 Patents (Medical) associated with Sm-14

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97

Literatures (Medical) associated with Sm-14

01 Jun 2023·PLoS neglected tropical diseases

Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells.

Article

Author: Gentenaar, Max ; van Hengel, Oscar R J ; Harvey, Michael R ; Chiodo, Fabrizio ; Hensbergen, Paul J ; Scheenstra, Maaike R ; Ozir-Fazalalikhan, Arifa ; Yazdanbakhsh, Maria ; Gasan, Thomas A ; van Diepen, Angela ; Chayé, Mathilde A M ; Heijke, Anouk M ; Smits, Hermelijn H ; Kalinowska, Alicja ; Codée, Jeroen D C ; Hokke, Cornelis H ; Guigas, Bruno ; Zawistowska-Deniziak, Anna ; Manurung, Mikhael D

During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a significant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (MW) range. The high MW fractions were rich in heavily glycosylated molecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo. Identification of unique Breg cells-inducing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.

01 Mar 2023·ERJ Open Research

Plasma sphingolipids, lung function and COPD: the Cardiovascular Health Study

Article

Author: Sitlani, Colleen M ; Psaty, Bruce M ; Sotoodehnia, Nona ; Jensen, Paul N ; Gharib, Arya R ; Lemaitre, Rozenn N ; Hoofnagle, Andrew N ; Gharib, Sina A ; Siscovick, David

RationaleCOPD is the third leading cause of death in the United States. Sphingolipids, structural membrane constituents that play a role in cellular stress and apoptosis signalling, may be involved in lung function.MethodsIn the Cardiovascular Health Study, a prospective cohort of older adults, we cross-sectionally examined the association of plasma levels of 17 sphingolipid species with lung function and COPD. Multivariable linear regression and logistic regression were used to evaluate associations of sphingolipid concentrations with forced expiratory volume in 1 s (FEV1) and odds of COPD, respectively.ResultsOf the 17 sphingolipids evaluated, ceramide-18 (Cer-18) and sphingomyelin-18 (SM-18) were associated with lower FEV1values (–0.061 L per two-fold higher Cer-18, p=0.001; −0.092 L per two-fold higher SM-18, p=0.002) after correction for multiple testing. Several other associations were significant at a 0.05 level, but did not reach statistical significance after correction for multiple testing. Specifically, Cer-18 and SM-18 were associated with higher odds of COPD (odds ratio per two-fold higher Cer-18 1.29, p=0.03 and SM-18 1.73, p=0.008). Additionally, Cer-16 and SM-16 were associated with lower FEV1values, and Cer-14, SM-14 and SM-16 with a higher odds of COPD.ConclusionIn this large cross-sectional study, specific ceramides and sphingomyelins were associated with reduced lung function in a population-based study. Future studies are needed to examine whether these biomarkers are associated with longitudinal change in FEV1within individuals or with incident COPD.

01 Jan 2023·Frontiers in microbiology

Purification and biochemical characterization of SM14est, a PET-hydrolyzing enzyme from the marine sponge-derived Streptomyces sp. SM14.

Article

Author: Schubert, Sune W ; Dobson, Alan D W ; Westh, Peter ; Clarke, David J ; Paul, Bijoya ; Clausen, Kristine S R ; Carr, Clodagh M ; Keller, Malene B ; Jensen, Kenneth

The successful enzymatic degradation of polyester substrates has fueled worldwide investigation into the treatment of plastic waste using bio-based processes. Within this realm, marine-associated microorganisms have emerged as a promising source of polyester-degrading enzymes. In this work, we describe the hydrolysis of the synthetic polymer PET by SM14est, a polyesterase which was previously identified from Streptomyces sp. SM14, an isolate of the marine sponge Haliclona simulans. The PET hydrolase activity of purified SM14est was assessed using a suspension-based assay and subsequent analysis of reaction products by UV-spectrophotometry and RP-HPLC. SM14est displayed a preference for high salt conditions, with activity significantly increasing at sodium chloride concentrations from 100 mM up to 1,000 mM. The initial rate of PET hydrolysis by SM14est was determined to be 0.004 s^-1 at 45°C, which was increased by 5-fold to 0.02 s^-1 upon addition of 500 mM sodium chloride. Sequence alignment and structural comparison with known PET hydrolases, including the marine halophile PET6, and the highly efficient, thermophilic PHL7, revealed conserved features of interest. Based on this work, SM14est emerges as a useful enzyme that is more similar to key players in the area of PET hydrolysis, like PHL7 and IsPETase, than it is to its marine counterparts. Salt-tolerant polyesterases such as SM14est are potentially valuable in the biological degradation of plastic particles that readily contaminate marine ecosystems and industrial wastewaters.

100 Deals associated with Sm-14

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Schistosomiasis Haematobia	Phase 2	SN	Fundação Oswaldo Cruz	01 Jul 2022
Schistosomiasis Mansoni	Phase 2	SN	Fundação Oswaldo Cruz	01 Jul 2022
Vaccination	Phase 2	SN	Fundação Oswaldo Cruz	01 Jul 2022
Schistosomiasis	Phase 2	-	Orygen Biotecnologia Ltda.	-