Biomedical subjects

J H Aberle

Publications and source records attributed to J H Aberle.

5 recordsLinked to original sources

PubMed2004

Decreased interferon-gamma response in respiratory syncytial virus compared to other respiratory viral infections in infants.

An inappropriate interferon-gamma response has been implicated in the pathogenesis of severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI). To assess whether this is unique for RSV primary LRTI compared to a first non-RSV LRTI, intracellular interferon-gamma was determined by flow cytometry in peripheral blood mononuclear cells from 32 infants with a primary RSV infection, 28 with a first non-RSV LRTI due to adenoviral, parainfluenzaviral and rhinoviral infection and 13 healthy infants. Interferon-gamma responses were increased significantly during adenoviral, parainfluenzaviral and the majority of the rhinoviral infections, but remained low during RSV and severe rhinoviral infection. Low interferon-gamma responses were associated with a more severe clinical course of LRTI. This indicates that depending on the nature of the viral pathogen, respiratory virus infections in infants differ significantly with regard to the quantity of the interferon-gamma production and that this may contribute to the clinical course of the disease.

Adenoviridae Infections↗

PubMed1999

A DNA immunization model study with constructs expressing the tick-borne encephalitis virus envelope protein E in different physical forms.

We have conducted a DNA immunization study to evaluate how the immune response is influenced by the physical structure and secretion of the expressed Ag. For this purpose, we used a series of plasmid constructs encoding different forms of the envelope glycoprotein E of the flavivirus tick-borne encephalitis virus. These included a secreted recombinant subviral particle, a secreted carboxyl-terminally truncated soluble homodimer, a nonsecreted full-length form, and an inefficiently secreted truncated form. Mice were immunized using both i.m. injection and Gene Gun-mediated application of plasmids. The functional immune response was evaluated by determining specific neutralizing and hemagglutination-inhibiting Ab activities and by challenging the mice with a lethal dose of the virus. As a measure for the induction of a Th1 and/or Th2 response, we determined specific IgG subclasses and examined IFN-gamma, Il-4, and Il-5 induction. The plasmid construct encoding a secreted subviral particle, which carries multiple copies of the protective Ag on its surface, was superior to the other constructs in terms of extent and functionality of the Ab response as well as protection against virus challenge. As expected, the type of Th response was largely dependent on the mode of application (i.m. vs Gene Gun), but our data show that it was also strongly influenced by the properties of the Ag. Most significantly, the plasmid encoding the particulate form was able to partially overcome the Th2 bias imposed by the Gene Gun, resulting in a balanced Th1/Th2 response.

Animals↗

PubMed1999

Nephropathia epidemica and Puumala virus in Austria.

To study the epidemiology of hantavirus infections in Austria, 1215 humans and 596 rodents of different species were tested for the presence of antibodies against Puumala and Hantaan virus. Direct virus identification by polymerase chain reaction in lung tissue of serologically positive rodents was performed to verify antibody results and to determine the genetic identity of viral RNA by phylogenetic analysis of a part of the hantavirus M segment. For 32 of the 37 cases of nephropathia epidemica diagnosed in Austria, the location where transmission took place could be traced to specific areas in the Austrian federal states of Carinthia and Styria. The overall seroprevalence in humans was 1.2% and ranged from 0.02% in Villach, Carinthia, to 0.8% in Korneuburg, Lower Austria, and 1.8% in Wolfsberg, Carinthia. Virus RNA could be amplified from three Clethrionomys glareolus voles collected in Klippitztörl, Carinthia, and from one collected in Ernstbrunn, Lower Austria. The sequences were all identified as Puumala virus by phylogenetic analysis and were found to be most closely related to the western European Puumala viruses from Germany and France. No evidence of the existence of Hantaan-like infections and viruses in Austria was found.

Animals↗

PubMed1999

Reduced interferon-gamma expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease.

We examined the in vivo cell-mediated immune response in infants with respiratory syncytial virus (RSV) infection in order to gain information about the pathogenesis of severe RSV disease in infancy. Semiquantitative reverse transcription-polymerase chain reaction and three-color flow cytometry were used to determine the levels of messenger RNA (mRNA) for interferon (IFN)-gamma in peripheral blood mononuclear cells, and the distribution of lymphocyte subsets in infants with acute RSV infection. The findings were correlated with the severity of the patients' illness and the production of RSV-specific IgE antibodies (RSV-IgE). Significantly lower IFN-gamma levels and T-lymphocyte counts in the acute phase of illness were observed in infants with severe RSV disease than in those with a milder clinical course of illness. The induction of RSV-IgE was not related to IFN-gamma levels in the acute phase of illness, but rather correlated with IFN-gamma expression during convalescence. The data indicate that reduced IFN-gamma expression may be an important factor in the pathogenesis of severe RSV disease in infancy.

Antibodies, Viral↗

PubMed1998

In vitro-synthesized infectious RNA as an attenuated live vaccine in a flavivirus model.

Live virus vaccines have in many cases proven to be an extremely effective tool for the prevention of viral diseases. However, the production of conventional live vaccines in eukaryotic cell cultures has many disadvantages, including the potential for contamination with adventitious agents and genetic alterations during propagation, making it necessary to do extensive testing before distribution. Based on results obtained with a flavivirus (tick-borne encephalitis virus) in an experimental animal system, we propose a novel live attenuated virus vaccination strategy consisting of the application of in vitro-synthesized infectious RNA instead of the live virus itself. When administered using the GeneGun, less than 1 ng of RNA was required to initiate replication of virus that was attenuated by a specifically engineered deletion and this induced a protective immunity in laboratory mice. Because this approach uses RNA, it does not have the potential drawbacks of DNA vaccines and thus combines the advantages of conventional live virus vaccines (for example, mimicking natural infection and inducing long-lasting immunity) with those of nucleic acid-based vaccines (for example, ease of production without a requirement for eukaryotic cell culture, stability and purity).

Animals↗