Marton A.,Hungarian Academy of Sciences |
Vizler C.,Hungarian Academy of Sciences |
Kusz E.,Hungarian Academy of Sciences |
Temesfoi V.,Hungarian Academy of Sciences |
And 13 more authors.
Immunology Letters | Year: 2012
To clarify controversies in the literature of the field, we have purified and characterized B16F1 melanoma cell derived exosomes (mcd-exosomes) then we attempted to dissect their immunological activities. We tested how mcd-exosomes influence CD4+ T cell proliferation induced by bone marrow derived dendritic cells; we quantified NF-κB activation in mature macrophages stimulated with mcd-exosomes, and we compared the cytokine profile of LPS-stimulated, IL-4 induced, and mcd-exosome treated macrophages. We observed that mcd-exosomes helped the maturation of dendritic cells, enhancing T cell proliferation induced by the treated dendritic cells. The exosomes also activated macrophages, as measured by NF-κB activation. The cytokine and chemokine profile of macrophages treated with tumor cell derived exosomes showed marked differences from those induced by either LPS or IL-4, and it suggested that exosomes may play a role in the tumor progression and metastasis formation through supporting tumor immune escape mechanisms. © 2012 Elsevier B.V.
Sollner J.,Emergentec Biodevelopment GmbH |
Heinzel A.,Emergentec Biodevelopment GmbH |
Heinzel A.,Upper Austria University of Applied Sciences |
Summer G.,Upper Austria University of Applied Sciences |
And 6 more authors.
Immunome Research | Year: 2010
Background. The last years have seen a renaissance of the vaccine area, driven by clinical needs in infectious diseases but also chronic diseases such as cancer and autoimmune disorders. Equally important are technological improvements involving nano-scale delivery platforms as well as third generation adjuvants. In parallel immunoinformatics routines have reached essential maturity for supporting central aspects in vaccinology going beyond prediction of antigenic determinants. On this basis computational vaccinology has emerged as a discipline aimed at ab-initio rational vaccine design. Here we present a computational workflow for implementing computational vaccinology covering aspects from vaccine target identification to functional characterization and epitope selection supported by a Systems Biology assessment of central aspects in host-pathogen interaction. We exemplify the procedures for Epstein Barr Virus (EBV), a clinically relevant pathogen causing chronic infection and suspected of triggering malignancies and autoimmune disorders. Results. We introduce pBone/pView as a computational workflow supporting design and execution of immunoinformatics workflow modules, additionally involving aspects of results visualization, knowledge sharing and re-use. Specific elements of the workflow involve identification of vaccine targets in the realm of a Systems Biology assessment of host-pathogen interaction for identifying functionally relevant targets, as well as various methodologies for delineating B- and T-cell epitopes with particular emphasis on broad coverage of viral isolates as well as MHC alleles. Applying the workflow on EBV specifically proposes sequences from the viral proteins LMP2, EBNA2 and BALF4 as vaccine targets holding specific B- and T-cell epitopes promising broad strain and allele coverage. Conclusion. Based on advancements in the experimental assessment of genomes, transcriptomes and proteomes for both, pathogen and (human) host, the fundaments for rational design of vaccines have been laid out. In parallel, immunoinformatics modules have been designed and successfully applied for supporting specific aspects in vaccine design. Joining these advancements, further complemented by novel vaccine formulation and delivery aspects, have paved the way for implementing computational vaccinology for rational vaccine design tackling presently unmet vaccine challenges. © 2010 Söllner et al.
Stipkovits L.,Carlsbad Research Organization |
Stipkovits L.,Europe Research Center |
Somogyi M.,Europe Research Center |
Somogyi M.,GalenBio Kft |
And 5 more authors.
Journal of Dairy Science | Year: 2013
We performed a comparative study on the development of mastitis induced by Mycoplasma arginini or Streptococcus dysgalactiae after challenging the cows. Mycoplasma arginini did not cause any clinical symptoms on its own, resulting in only a transient increase of somatic cell count (SCC; increase ranging from 0.5×106 to 0.8×106 cells/mL) and a slight decrease of milk production (10%) for 5 d. In contrast, Strep. dysgalactiae induced more severe clinical signs in animals and SCC increased to 1.60×106 to 2.11×106 cells/mL for 10 d. In addition, milk production decreased (22.9 to 27.0%) for 10 d. After 3mo (2mo after the first challenge), animals that were challenged previously with M. arginini were rechallenged with Strep. dysgalactiae. Severe clinical mastitis developed, with very high SCC (5.00×106 to 21.5×106 cells/mL), and a very significant reduction of milk production (28.6 to 68.7%), which lasted more than 4wk, was observed. The severe clinical mastitis developed not only in cows inoculated with Strep. dysgalactiae andM. arginini in the same udder quarter but also in cows infected in the quarter previously not challenged with mycoplasma. Cows challenged first with Strep. dysgalactiae and rechallenged with M. arginini 2mo later developed only slight changes in both SCC and milk production, similar to those when the cows were challenged with M. arginini alone. We conclude that M. arginini infection does not cause remarkable mastitis (characterized by decrease in milk production and increase of SCC) but it significantly predisposes animals to infection with Strep. dysgalactiae, leading to severe clinical mastitis. © 2013 American Dairy Science Association.