Dataset Information

Intranasal administration of cationic liposomes enhanced granulocyte-macrophage colony-stimulating factor expression and this expression is dispensable for mucosal adjuvant activity.

ABSTRACT: Infectious diseases remain a threat to human life. Vaccination against pathogenic microbes is a primary method of treatment as well as prevention of infectious diseases. Particularly mucosal vaccination is a promising approach to fight against most infectious diseases, because mucosal surfaces are a major point of entry for most pathogens. We recently developed an effective mucosal adjuvant of cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3?-[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposomes). However, the mechanism(s) underlying the mucosal adjuvant effects exerted by the cationic liposomes have been unclear. In this study, we investigated the role of granulocyte-macrophage colony-stimulating factor (GM-CSF), which was reported to act as a mucosal adjuvant, on the mucosal adjuvant activities of DOTAP/DC-chol liposomes when administered intranasally to mice.Here, we show that, although intranasal vaccination with cationic liposomes in combination with antigenic protein elicited GM-CSF expression at the site of administration, blocking GM-CSF function by using an anti-GM-CSF neutralizing antibody did not alter antigen-specific antibody production induced by DOTAP/DC-chol liposomes, indicating that GM-CSF may not contribute to the mucosal adjuvant activity of the cationic liposomes when administered intranasally.

SUBMITTER: Tada R

PROVIDER: S-EPMC6045820 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Intranasal administration of cationic liposomes enhanced granulocyte-macrophage colony-stimulating factor expression and this expression is dispensable for mucosal adjuvant activity.

Tada Rui R Hidaka Akira A Kiyono Hiroshi H Kunisawa Jun J Aramaki Yukihiko Y

BMC research notes 20180713 1

<h4>Objective</h4>Infectious diseases remain a threat to human life. Vaccination against pathogenic microbes is a primary method of treatment as well as prevention of infectious diseases. Particularly mucosal vaccination is a promising approach to fight against most infectious diseases, because mucosal surfaces are a major point of entry for most pathogens. We recently developed an effective mucosal adjuvant of cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3 ...[more]

PMID: 30005702

Similar Datasets

Project description:The human granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor used to prevent and treat neutropenia. G-CSF stimulates the bone marrow to produce infection-fighting granulocytes. Food and Drug Administration of the United States approved G-CSF in 1991 and its PEGylated version in 2002 as a prophylactic and therapeutic measure against neutropenia. Recombinant human G-CSF is produced in surrogate host Escherichia coli and is PEGylated at N-terminal. Besides neutropenia, G-CSF is also used in bone marrow transplantation for the mobilization and maturation of peripheral blood stem cells. Considering the requirement of producing G-CSF therapeutic in large quantities, construct designing for high expression is critical for the biopharmaceutical and industrial application. Earlier studies have employed approaches such as codon optimization, use of strong promoters, employment of protein tags, secretion signals, optimization of protein folding, etc., for increasing expression and yield of therapeutic proteins. In this study, it was observed that mRNA transcribed from the native human cDNA of G-CSF and the codon-optimized variant leads to low protein expression in E. coli. To understand the underlying reasons, the mRNA secondary structure of the 5' end of the G-CSF transcript was analyzed. This analysis revealed the presence of stable secondary structures at the 5' end of the G-CSF transcript, arising from the native human gene and even from the codon-optimized sequence. These secondary structures were disrupted through translationally silent mutations within the first 24 nucleotides of the transcript without affecting the protein sequence. Interestingly, through this approach, the G-CSF protein expression was increased 60 folds as compared to native G-CSF construct. We believe that these findings create a roadmap for optimization of G-CSF transcript for enhanced expression in E. coli and could be employed to increase the expression of other therapeutic proteins.

Dataset Information

Intranasal administration of cationic liposomes enhanced granulocyte-macrophage colony-stimulating factor expression and this expression is dispensable for mucosal adjuvant activity.

Publications

Intranasal administration of cationic liposomes enhanced granulocyte-macrophage colony-stimulating factor expression and this expression is dispensable for mucosal adjuvant activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets