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Tregoning J.S.,Imperial College London | Buffa V.,Cell Medica | Oszmiana A.,Manchester Collaborative Center for Inflammation Research | Klein K.,Imperial College London | And 2 more authors.
PLoS ONE | Year: 2013

One potential strategy for the prevention of HIV infection is to induce virus specific mucosal antibody that can act as an immune barrier to prevent transmission. The mucosal application of chemokines after immunisation, termed "prime-pull", has been shown to recruit T cells to mucosal sites. We wished to determine whether this strategy could be used to increase B cells and antibody in the vaginal mucosa following immunisation with an HIV antigen. BALB/c mice were immunised intranasally with trimeric gp140 prior to vaginal application of the chemokine CCL28 or the synthetic TLR4 ligand MPLA, without antigen six days later. There was no increase in vaginal IgA, IgG or B cells following the application of CCL28, however vaginal application of MPLA led to a significant boost in antigen specific vaginal IgA. Follow up studies to investigate the effect of the timing of the "pull" stimulation demonstrated that when given 14 days after the initial immunisation MPLA significantly increased systemic antibody responses. We speculate that this may be due to residual inflammation prior to re-immunisation. Overall we conclude that in contrast to the previously observed effect on T cells, the use of "prime-pull" has only a modest effect on B cells and antibody. © 2013 Tregoning et al. Source


Jegerlehner A.,Cytos Biotechnology AG | Zabel F.,Cytos Biotechnology AG | Zabel F.,University of Zurich | Langer A.,Cytos Biotechnology AG | And 6 more authors.
PLoS ONE | Year: 2013

Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains. © 2013 Jegerlehner et al. Source


News Article
Site: http://www.biosciencetechnology.com/rss-feeds/all/rss.xml/all

An interdisciplinary team of Oxford University researchers has devised a new technique to speed up the development of novel vaccines. Many vaccines are based around virus-like particles (VLPs). VLPs resemble viruses, but importantly don't carry pathogenic genetic material and thus cannot cause disease. These particles are engineered to display one part of a pathogen to the immune system, which can elicit strong protection upon any subsequent exposure to that pathogen. Karl Brune, leading the work in Professor Mark Howarth's lab in Oxford’s Department of Biochemistry explained: 'Current techniques to develop VLP-based vaccines take time and do not always work. Whilst getting the pathogen parts to stick to the carrier VLP, often problems such as misassembly or misfolding arise that make the vaccine ineffective at generating protective immunity.' This failure rate translates into high development costs in trying to create vaccines against major diseases such as malaria, HIV and cancer. 'A more reliable way of assembling candidate vaccines could make them much cheaper and improve the chances of vaccines against these illnesses. A faster way of assembling vaccines may also help with the rapid development of new vaccines against unforeseen disease outbreaks.', said Dr. Darren Leneghan, leading the immunisation work with Dr. Sumi Biswas and Professor Simon Draper in Oxford's Jenner Institute, which specialises in vaccine development. Karl Brune’s work has now overcome this key challenge in vaccine assembly using the lab's 'bacterial superglue'. This glue is made of two parts, a larger protein called SpyCatcher and a smaller protein part named SpyTag, both engineered from the bacterium Streptococcus pyogenes. When SpyTag and SpyCatcher meet, they form an unbreakable bond. The team succeeded in biologically encoding SpyCatcher on VLPs, which now enables scientists and engineers easily and relatively quickly to glue proteins with the small SpyTag to the SpyCatcher-VLPs. Karl Brune said: ‘We tested the SpyCatcher-VLP – SpyTag-antigen combination using a range of malarial and cancer-relevant antigens. This showed that linking can be done simply and quickly to produce stable vaccines that generated robust antibody responses. 'We need to do more research, both to see if we can use Tag/Catcher fusion with other diseases and to test effectiveness in live rather than lab conditions.' The team say that their technique should speed up developing new vaccines and also may help other medical applications of nanoparticles.


Vainieri M.L.,Imperial College London | Blagborough A.M.,Imperial College London | MacLean A.L.,Imperial College London | Haltalli M.L.R.,Imperial College London | And 7 more authors.
Open Biology | Year: 2016

Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, nonlethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1+ progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host. © 2016 The Authors. Source


News Article
Site: http://phys.org/biology-news/

Many vaccines are based around virus-like particles (VLPs). VLPs resemble viruses, but importantly don't carry pathogenic genetic material and thus cannot cause disease. These particles are engineered to display one part of a pathogen to the immune system, which can elicit strong protection upon any subsequent exposure to that pathogen. Karl Brune, leading the work in Professor Mark Howarth's lab in Oxford's Department of Biochemistry explained: 'Current techniques to develop VLP-based vaccines take time and do not always work. Whilst getting the pathogen parts to stick to the carrier VLP, often problems such as misassembly or misfolding arise that make the vaccine ineffective at generating protective immunity.' This failure rate translates into high development costs in trying to create vaccines against major diseases such as malaria, HIV and cancer. 'A more reliable way of assembling candidate vaccines could make them much cheaper and improve the chances of vaccines against these illnesses. A faster way of assembling vaccines may also help with the rapid development of new vaccines against unforeseen disease outbreaks.', says Dr Darren Leneghan, leading the immunisation work with Dr Sumi Biswas and Professor Simon Draper in Oxford's Jenner Institute, which specialises in vaccine development. Karl Brune's work has now overcome this key challenge in vaccine assembly using the lab's 'bacterial superglue'. This glue is made of two parts, a larger protein called SpyCatcher and a smaller protein part named SpyTag, both engineered from the bacterium Streptococcus pyogenes. When SpyTag and SpyCatcher meet, they form an unbreakable bond. The team succeeded in biologically encoding SpyCatcher on VLPs, which now enables scientists and engineers easily and relatively quickly to glue proteins with the small SpyTag to the SpyCatcher-VLPs. Karl Brune said: 'We tested the SpyCatcher-VLP – SpyTag-antigen combination using a range of malarial and cancer-relevant antigens. This showed that linking can be done simply and quickly to produce stable vaccines that generated robust antibody responses. 'We need to do more research, both to see if we can use Tag/Catcher fusion with other diseases and to test effectiveness in live rather than lab conditions.' The team say that their technique should speed up developing new vaccines and also may help other medical applications of nanoparticles. Explore further: Combination vaccine protects monkeys from ebola and Marburg viruses More information: Karl D. Brune et al. Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization, Scientific Reports (2016). DOI: 10.1038/srep19234

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