Biomedical subjects

Roman Bauer

Publications and source records attributed to Roman Bauer.

5 recordsLinked to original sources

PubMed2006

Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive and therapeutic effects in a mouse model of allergy.

BACKGROUND: Hypoallergenic immunotherapy of type I allergies aims at inducing T-cell immunity while avoiding cross-linking of pre-existing IgE. DNA-based immunotherapy depends on the recruitment of antigen-specific T(H)1 cells and therefore has to provide the whole repertoire of T-cell epitopes. Ubiquitination offers a general approach for the production of hypoallergenic DNA vaccines. OBJECTIVE: A DNA-based vaccine encoding the major birch pollen allergen Bet v 1 stably linked to ubiquitin was evaluated for its antiallergic potential in a BALB/c mouse model of allergy. METHODS: Plasmid DNA was applied to mice before (preventive) or after (therapeutic) sensitization with recombinant Bet v 1. In the preventive setting, mice were exposed to aerosolized allergen in addition. Cytokine production was monitored via ELISPOT and Luminex. IgG(1), IgG(2a), and IgE subclass antibody titers were determined by ELISA. In vitro antigen-specific cross-linking of IgE was measured in a degranulation assay. Bronchoalveolar lavages were analyzed for leukocyte subsets as well as for IFN-gamma and IL-5, and paraffin sections of lungs were examined for mucus production and endothelial damage. RESULTS: Prevaccination with ubiquitinated Bet v 1-stimulated T(H)1-biased immune responses with concomitant suppression of functional IgE, reduction of eosinophil counts in bronchoalveolar lavages, and alleviation of lung pathology, and could also suppress an ongoing IgE response in a therapeutic setting. CONCLUSION: The data clearly demonstrate that hypoallergenic DNA vaccines encoding ubiquitin fusion constructs induce effective antiallergic immune responses. CLINICAL IMPLICATIONS: Ubiquitination of allergen gene vaccines eliminates the risk of IgE cross-linking, thereby meeting the safety requirements for clinical applications.

Allergens↗

PubMed2003

Strategies for the development of safe and effective DNA vaccines for allergy treatment.

During the past ten years, a great number of studies have demonstrated that injection of plasmid DNA coding for certain genes results in the induction of humoral and cellular immune responses against the respective gene product. The features of DNA vaccines enable a broad range of applications, including the induction of protective immunity against viral, bacterial, and parasitic infections, and open up new perspectives for the treatment of cancer. Furthermore, based on their Th1-promoting properties, DNA vaccines also turned out to balance Th2-mediated immune reactions, a quality which renders them a promising alternative for immunotherapy against allergy. Their unique immunological properties offer new possibilities for the development of vaccines, which do not cause anaphylactic side effects, a major drawback of specific immunotherapy (SIT). In this review, we present approaches to avoid the translation of native allergenic determinants, thus preventing release of allergy mediators stimulated by crosslinking of pre-existing or vaccine-induced IgE antibodies on mast cells. Three approaches are described, which fulfill these requirements: (i) cutting the allergen gene into overlapping fragments, which lack any antigenic determinant of the native allergen, but display the original repertoire of T cell epitopes, (ii) using hypoallergenic derivatives or (iii) fusing the allergen with ubiquitin, thus fragmenting the antigen and destroying its native structure. The presented experiments demonstrate that DNA vaccines are suitable to balance an allergic response in a protective as well as a therapeutic experimental design, thus demonstrating their potential for allergy treatment. In addition to conventional plasmid DNA vaccines, aspects and perspectives of replicon-based DNA vaccines will be discussed.

Allergens↗

PubMed2002

Perceptual grouping correlates with short synchronization in monkey prestriate cortex.

Synchronization in the visual cortex at 35-80 Hz is assumed to support perceptual grouping. We tested this hypothesis in a figure-ground task in which a trained monkey indicated by a key whether he perceived a figure that was composed of the same blobs as the background distractors. The task was sufficiently difficult such that about 25% of responses were incorrect. We recorded population activity with 7 microelectrodes in prestriate cortex (V2). During a short period before the monkey's perceptual response, locations of figure-activated neurons showed increased synchronization (50-80 Hz) in correct compared to incorrect responses, while other signal measures were unrelated to perception. These are first indications that a short synchronous burst in V2 may support perceptual grouping.

Action Potentials↗

PubMed2002

Contour integration in striate cortex. Classic cell responses or cooperative selection?

Psychophysics has established various rules of contour integration in gestalt perception. We tested the rule of good continuation by stimulating behaving monkeys with simple figures composed of Gabor patches, while recording from upper layer cells in visual cortex (V1). By decomposing these figures into their components and stimulating receptive field centers and surrounds separately with this stimulus set, we tested center-surround interaction for linearity. In pure-fixation tasks, the interaction was negative for the early strong evoked response, i.e., in this phase figural context rather inhibited the cells. However, in the following tonic response phase, a subgroup of neurons showed positive interaction during the whole stimulus presentation period of at least 1,000 ms. Attention to the figure in discrimination tasks only slightly improved this positive interaction between 150 and 300 ms. We interpret these results as selective cooperation and mutual facilitation of cortical V1 cells, thereby supporting the saliency of borders and contours in perception of visual scenes.

Animals↗

PubMed2002

Inter-cellular spike coincidences in visual detection tasks.

Synchronized spike activity is discussed as a possible representational code for object integration and as a neuronal basis of attention, perception and awareness. As a byproduct of experiments in which monkeys were trained to detect simple figures composed of single Gabor patches in a noisy background of similar elements, we found in special cases increased spike synchrony above chance level specifically related to figure detection. The long latency of this effect is difficult to interpret. It may be a sign of the cognitive state of an animal when it perceives the figure.

Animals↗