Biomedical subjects

Tanja Breinig

Publications and source records attributed to Tanja Breinig.

4 recordsLinked to original sources

PubMed2006

The Autographa californica nuclear polyhedrosis virus AcNPV induces functional maturation of human monocyte-derived dendritic cells.

The initiation of an adaptive immune response is critically dependent on the activation of dendritic cells (DCs). Therefore, vaccination strategies targeting DCs have to ensure a proper presentation of the immunogen as well as an activation of DCs to accomplish their full maturation. Viral vectors can achieve gene delivery and a subsequent presentation of the expressed immunogen, however, the immunization efficiency may be hampered by an inhibition of DC activation. Here we report that the insect born Autographa californica nuclear polyhedrosis virus (AcNPV), which is already used for genetic immunization, is able to activate human monocyte-derived DCs. This activation induces the production of tumor necrosis factor alpha (TNF-alpha), an up-regulation of the surface molecules CD83, CD80, CD86, HLA-DR and HLA-I and increases the T cell stimulatory capacity of DCs. Thus, AcNPV represents a promising vector for vaccine trials.

Antibodies, Blocking↗

PubMed2006

Cross-presentation of HLA class I epitopes from influenza matrix protein produced in Saccharomyces cerevisiae.

Here we report that genetically engineered yeast of the strain Saccharomyces cerevisiae expressing full-length influenza matrix protein (IMP) attached to the yeast cell wall are a very versatile host for antigen delivery. Feeding of dendritic cells with either intact yeast expressing IMP protein or soluble IMP protein cleaved off the cell wall resulted in protein uptake, processing and cross-presentation of IMP-derived peptides. This process was analysed using previously established T-cell lines recognizing the immuno-dominant 58-66 peptide when presented by HLA-A2*0201 complexes. In addition, IMP(58-66)/HLA-A2*0201-specific antibodies were selected from a naive phage library which confirmed that peptide presentation was an active process of endocellular uptake and not just a result of external peptide loading. Moreover, MHC peptide antibodies could block the recognition of peptide-presenting dendritic cells by IMP(58-66)-specific T-cells in a dose dependent manner. There was no difference in T-cell recognition when either intact yeast or yeast cell extracts were used for DC feeding. Together, these data demonstrate that yeast derived proteins either in their soluble form or as part of a whole yeast vaccine are taken up, processed and presented by dendritic cells in HLA class I context.

Antibody Specificity↗

PubMed2006

Antigen-specific T cell responses: determination of their frequencies, homing properties, and effector functions in human whole blood.

Several prevalent and life-threatening agents enter the organism via the mucosa. In this case, a mucosal cellular immune response is essential for protection and is therefore considered the main objective of vaccination. The frequency of antigen-specific CD4+ and CD8+ T cells can be determined directly in human whole blood by a combination of surface marker and intracellular cytokine staining. Immune cells primed in the mucosal compartment also migrate through the blood and can be identified by expression of the gut-specific homing receptor alpha4beta7. Simultaneously, these lymphocytes can be functionally characterized regarding their differentiation status by analysis of CD45RO and CD27 expression and effector functions by measuring intracellular perforin or granzyme B content. Thus, the technique described in the paper is a powerful tool for clinical monitoring of the total cellular immune response to complex antigens during infection or vaccination.

Antigens↗

PubMed2005

A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination.

It has been previously shown that the majority of human immunodeficiency virus type 1 (HIV-1)-infected splenocytes can harbour multiple, divergent proviruses with a copy number ranging from one to eight. This implies that, besides point mutations, recombination should be considered as an important mechanism in the evolution of HIV within an infected host. To explore in detail the possible contributions of multi-infection and recombination to HIV evolution, the effects of major microscopic parameters of HIV replication (i.e. the point-mutation rate, the crossover number, the recombination rate and the provirus copy number) on macroscopic characteristics (such as the Hamming distance and the abundance of n-point mutants) have been simulated in silico. Simulations predict that multiple provirus copies per infected cell and recombination act in synergy to speed up the development of sequence diversity. Point mutations can be fixed for some time without fitness selection. The time needed for the selection of multiple mutations with increased fitness is highly variable, supporting the view that stochastic processes may contribute substantially to the kinetics of HIV variation in vivo.

Algorithms↗