Molecular Microbiology Group

Southampton, United Kingdom

Molecular Microbiology Group

Southampton, United Kingdom

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Seth-Smith H.M.B.,Wellcome Trust Sanger Institute | Harris S.R.,Wellcome Trust Sanger Institute | Rance R.,Wellcome Trust Sanger Institute | West A.P.,Wellcome Trust Sanger Institute | And 9 more authors.
Journal of Bacteriology | Year: 2011

We present the first genome sequence of Chlamydophila psittaci, an intracellular pathogen of birds and a human zoonotic pathogen. A comparison with previously sequenced Chlamydophila genomes shows that, as in other chlamydiae, most of the genome diversity is restricted to the plasticity zone. The C. psittaci plasmid was also sequenced. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

PubMed | Vaccinology and Vaccine Immunology Group and Molecular Microbiology Group
Type: Journal Article | Journal: Microbiology and immunology | Year: 2016

Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN- and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA+ CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA+ CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA+ CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA+ CT vaccine enhanced not only IFN- but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB.

Miyata T.,Molecular Microbiology Group | Harakuni T.,Molecular Microbiology Group | Tsuboi T.,Ehime University | Sattabongkot J.,Armed Forces Research Institute of Medical science | And 8 more authors.
Infection and Immunity | Year: 2011

The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker. The vaccine efficacy of the tricomponent complex was evaluated using an ookinete surface protein of Plasmodium vivax, Pvs25, and merozoite surface protein-1 of Plasmodium yoelii. Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels of P. vivax transmission blockade as evaluated by a membrane feed assay, as well as protection from lethal P. yoelii infection. The observed effect was strongly dependent on the presence of all three components physically integrated as a fusion complex. This system, designated the tricomponent immunopotentiating system (TIPS), onto which any recombinant protein antigens or nonproteinaceous substances could be loaded, may be a promising strategy for devising subunit vaccines or adjuvants against various infectious diseases, including malaria. © 2011, American Society for Microbiology.

Agency: Narcis | Branch: Project | Program: Completed | Phase: Physics, Chemistry and Medicine | Award Amount: | Year: 2007

Most of the therapeutic proteins (e.g. antibodies and hormones) are proteins that are secreted by human cells via the secretory pathway. Many of these therapeutic proteins are glycosylated during passage through this pathway and the glycans on the protein often play a crucial role in their pharmacological properties. At the moment, therapeutic proteins are produced in mammal cell lines. Construction of these lines is complex and culturing expensive. Mushroom forming basidiomycetes are interesting candidates for the efficient production of therapeutic glycoproteins. They have a glycosylation pattern which is more similar to that of humans than that of plants and other fungi. Within this project we will improve heterologous protein production in mushroom and will further humanize its glycosylation machinery.

PubMed | Molecular Microbiology Group
Type: Journal Article | Journal: Microbiology and immunology | Year: 2013

An engineered bio-nanocapsule (BNC) comprising modified hepatitis B surface antigen L protein was used as a physical scaffold for envelope protein domain III (D3) of Japanese encephalitis virus (JEV). At the N terminus, the BNC contained a two-tandem repeat of the Z domain (ZZ) derived from Staphylococcus aureus protein A (ZZ-BNC). The Lys-rich ZZ moiety exposed on the surface of ZZ-BNC was used for chemical conjugation with the JEV D3 antigen, which had been expressed and purified from Escherichia coli. Immunization of mice with D3 loaded on the surface of ZZ-BNC (ZZ-BNC:D3) augmented serum IgG response against JEV and increased protection against lethal JEV infection. The present study suggests that innocuous recombinant antigens, when loaded on the surface of ZZ-BNC, can be transformed to immunogenic antigens.

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