Biomedical subjects

Ania Skowera

Publications and source records attributed to Ania Skowera.

3 recordsLinked to original sources

PubMed2006

Long-lasting T cell responses to biological warfare vaccines in human vaccinees.

BACKGROUND: Medical countermeasures against biological warfare include the use of vaccines for anthrax and plague, which require repeated dosing and adjuvant to achieve adequate protection from threats such as inhalational anthrax and pneumonic plague. Despite the widespread use of these measures in preparation for recent military deployments, little is known about the cell-mediated immune response that is induced by these vaccines, in comparison with conventional vaccines, such as pertussis or tetanus-diphtheria vaccines. METHODS: To examine this question, we used cytokine enzyme-linked immunospot assays to measure interferon-gamma, interleukin (IL)-2, IL-4, and IL-13-producing cells in military service personnel vaccinated during the Gulf War of 1990-1991. RESULTS: Our data indicate that 12-15 years after vaccination against anthrax and plague, antigen-specific T cell recall responses are present in the circulation and are comparable in magnitude to those for tetanus-diphtheria toxoids. Recall responses to anthrax were an approximately equal mixture of type 1 T helper cell (interferon-gamma and IL-2) and type 2 T helper cell (predominantly IL-13) responses, whereas plague cellular immunity was more polarized toward type 1 T helper cell responses. Responder cell frequency and type were similar to that against conventional tetanus-diphtheria (mixed type 1 and type 2 T helper cells) vaccine. When veterans were divided according to whether or not they reported multisymptom illness, there was no difference in the frequency or type of cellular response, although the number of cases in each group was small, and these data should be interpreted as preliminary. CONCLUSIONS: This study shows that, despite any putative limitations of vaccines for anthrax and plague in terms of achieving protective host immunity, long-lasting cell-mediated responses are generated with these agents.

Anthrax↗

PubMed2006

Immunological dysfunction, vaccination and Gulf War illness.

One candidate cause of Gulf War illness is vaccination against infectious diseases including medical counter-measures against biological weapons. One influential theory has suggested that such mass-vaccination caused a shift in immune response to a Type 2 cytokine pattern (Th2), which it was suggested was accompanied by a chronic fatigue syndrome-like illness. This article critically appraises this theory. We start by examining epidemiological evidence, which indicates that single vaccines are unlikely to be a substantial cause of Gulf War illness, but that there was a modest relationship with multiple vaccines, which was strongest in those vaccinated while deployed to the Gulf. These relationships may be affected by recall bias. We conclude by examining the results of immunological studies carried out in veterans or in a relevant setting in vitro. The balance of evidence from immunological studies on veterans returning from the War, including those developing multi-symptom illness, is that the immune response has not become polarized towards Th2. In summary, the epidemiological evidence for a multiple vaccine effect on Gulf War-related illness remains a potentially important aetiological lead, but mechanistic studies available at this stage do not identify any immunological basis for it.

Cytokines↗

PubMed2004

Identification of a naturally processed cytotoxic CD8 T-cell epitope of coxsackievirus B4, presented by HLA-A2.1 and located in the PEVKEK region of the P2C nonstructural protein.

The adaptive immune system generates CD8 cytotoxic T lymphocytes (CTLs) as a major component of the protective response against viruses. Knowledge regarding the nature of the peptide sequences presented by HLA class I molecules and recognized by CTLs is thus important for understanding host-pathogen interactions. In this study, we focused on identification of a CTL epitope generated from coxsackievirus B4 (CVB4), a member of the enterovirus group responsible for several inflammatory diseases in humans and often implicated in the triggering and/or acceleration of the autoimmune disease type 1 diabetes. We identified a 9-mer peptide epitope that can be generated from the P2C nonstructural protein of CVB4 (P2C(1137-1145)) and from whole virus by antigen-presenting cells and presented by HLA-A2.1. This epitope is recognized by effector memory (gamma interferon [IFN-gamma]-producing) CD8 T cells in the peripheral blood at a frequency of responders that suggests that it is a major focus of the anti-CVB4 response. Short-term CD8 T-cell lines generated against P2C(1137-1145) are cytotoxic against peptide-loaded target cells. Of particular interest, the epitope lies within a region of viral homology with the diabetes-related autoantigen, glutamic acid decarboxylase-65 (GAD(65)). However, P2C(1137-1145)-specific cytotoxic T lymphocyte (CTL) lines were not activated to produce IFN-gamma by the GAD(65) peptide homologue and did not show cytotoxic activity in the presence of appropriately labeled targets. These results describe the first CD8 T-cell epitope of CVB4 that will prove useful in the study of CVB4-associated disease.

Amino Acid Sequence↗