Escherichia coli-derived outer membrane vesicles deliver galactose-1-phosphate uridyltransferase and yield partial protection against Actinobacillus pleuropneumoniae in mice

Q4 · ENGINEERING & TECHNOLOGY

Article

Author: Yan, Qigui ; Huang, Yong ; Zhang, Fei ; Zhao, Qin ; Cao, Sanjie ; Miao, Chang ; Wu, Rui ; Wen, Xintian ; Huang, Xiaobo ; Quan, Keji ; Ma, Xiaoping ; Han, Xinfeng ; Zhu, Zhuang ; Wen, Yiping

In our previous studies, we have identified several in vivo-induced antigens and evaluated their potential as subunit vaccine candidates in a murine model, in which the recombinant protein GalT showed the most potent immunogenicity and immunoprotective efficacy against Actinobacillus pleuropneumoniae. To exploit a more efficient way of delivering GalT proteins, in this study, we employed the widely studied E. coli outer membrane vesicles (OMVs) as a platform to deliver GalT protein and performed the vaccine trial using the recombinant GalT-OMVs in the murine model. Results revealed that GalT-OMVs could elicit a highly-specific, IgG antibody titer that was comparable with the adjuvant GalT group. Significantly higher lymphocyte proliferation and cytokines secretion levels were observed in the GalT-OMVs group. 87.5% and 50% of mice were protected from a lethal dose challenge using A. pleuropneumoniae in active or passive immunization, respectively. Histopathologic and immunohistochemical analyses showed remarkably reduced pathological changes and infiltration of neutrophils in the lungs of mice immunized with GalT-OMVs after the challenge. Taken together, these findings confirm that OMVs can be used as a platform to deliver GalT protein and enhance its immunogenicity to induce both humoral and cellular immune responses in mice.

01 Dec 2016·Neurology Neuroimmunology & NeuroinflammationQ1 · MEDICINE

Induction of gut regulatory CD39 ⁺ T cells by teriflunomide protects against EAE

Q1 · MEDICINE

ArticleOA

Author: Colpitts, Sara L ; Telesford, Kiel M ; Begum-Haque, Sakhina ; Ochoa-Repáraz, Javier ; Kasper, Lloyd H ; Pant, Anudeep ; Kasper, Eli J ; Kircher, Christopher

OBJECTIVETo determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally.METHODSC57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells.RESULTSTeriflunomide reduced the percentages of antigen-presenting cells of Peyer patches when compared to controls. Conversely, a significant increase of the relative frequency of CD39⁺ Treg cells was observed. In vivo, the protective effect of GALT-derived teriflunomide-induced CD39⁺ Treg cells was established by adoptive transfer into recipient experimental autoimmune encephalomyelitis mice.CONCLUSIONSOur results identify specific GALT-derived CD39⁺ Treg cells as a mechanism of action that may contribute to the efficacy of teriflunomide during CNS inflammatory demyelination and as an oral therapeutic in relapsing multiple sclerosis.

01 Jan 2005·Medical HypothesesQ4 · MEDICINE

The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: A possible cause for poor long-term prognosis in classic galactosemia

Q4 · MEDICINE

Article

Author: Pieter J. Pretorius ; Phiyani Justice Lebea

Classic galactosemia is an autosomal recessive disorder that is caused by activity deficiency of the UDP-galactose uridyl transferase (GALT). The clinical spectrum of classic galactosemia differs according to the type and number of mutations in the GALT gene. Short-term clinical symptoms such as jaundice, hepatomegaly, splenomegaly and E. coli sepsis are typically associated with classic galactosemia. These symptoms are often severe but quickly ameliorate with dietary restriction of galactose. However, long-term symptoms such as mental retardation and primary ovarian failure do not resolve irrespective of dietary intervention or the period of initial dietary intervention. There seem to be an association between deficient galactosylation of cerebrosides and classic galactosemia. Galactocerebrosides and glucocerebrosides are the primary products of the enzyme UDP-galactose:cerebroside galactosyl transferase (CGT). There has been an observation of deficient galactosylation coupled with over glucosylation in the brain tissue specimens sampled from deceased classic galactosemia patients. The plausible mechanism with which the association between GALT and CGT had not been explained before. Yet, UDP-galactose serves as the product of GALT as well as a substrate for CGT. In classic galactosemia, there is a consistent deficiency in cerebroside galactosylation. We postulate that the molecular link between defective GALT enzyme, which result in classic galactosemia; and the cerebroside galactosyl transferase, which is responsible for galactosylation of cerebrosides is dependent on the cellular concentrations of UDP-galactose. We further hypothesize that a threshold concentration of UDP-galactose exist below which the integrity of cerebroside galactosylation suffers.

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Indication	Highest Phase	Country/Location	Organization	Date
Galactosemias	Preclinical	US	Pfizer Inc.	-

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