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Biomedical subjects

D Drane

Publications and source records attributed to D Drane.

13 recordsLinked to original sources
PubMed2004

ISCOMATRIX adjuvant: a potent inducer of humoral and cellular immune responses.

ISCOMATRIX adjuvant is capable of inducing broad and potent humoral and cellular immune responses. The components are well defined and the manufacturing process is simple and robust. Many vaccines containing the ISCOMATRIX adjuvant have been tested in a range of animal models, including human and non-human primates. Strong antibody and T cell responses have been induced in these studies. The antibody response is often achieved with lesser amounts of antigen than other adjuvant systems and the maximal responses have also been reached more quickly. Both CD4+ and CD8+ T cell responses are induced with the cytotoxic T lymphocyte responses being very long lived. Additionally, ISCOMATRIX adjuvant can be used in vaccines for induction of mucosal immune responses. This review provides an overview of the immune responses that can be elicited using ISCOMATRIX vaccines and the current state of knowledge regarding the mechanism of action of this adjuvant.

Adjuvants, Immunologic↗
PubMed2001

Local immune responses to influenza antigen are synergistically enhanced by the adjuvant ISCOMATRIX.

The peripheral (draining) lymph node, as the primary site of immune induction, determines the course of systemic responses to an injected antigen. Lymphatic duct cannulation procedures in sheep were used to investigate local immunoreactivity to human influenza virus antigen (Flu ag) admixed with the adjuvant ISCOMATRIX (IMX). Compared to Flu ag or IMX alone, the co-administration of Flu ag and IMX (Flu ag+IMX) synergistically enhanced a number of immunological responses (lymphocyte and blast migration from the node, antigen-specific antibody levels and IL6 output in efferent lymph, and antigen-induced proliferation in cultured efferent lymph cells). Together, these results demonstrate that IMX is an immune modulator, and that lymphatic duct cannulation procedures may be used to evaluate antigen/adjuvant combinations for vaccine development.

Adjuvants, Immunologic↗
PubMed2001

Cytotoxic T cell polyepitope vaccines delivered by ISCOMs.

CD8 alphabeta cytotoxic T lymphocyte (CTL) polyepitope or polytope vaccines have traditionally been delivered using recombinant vector or DNA based delivery modalities. Here we show the delivery of polytope vaccines in the form of either synthetic polypeptides or recombinant polytope proteins by ImmunoStimulatory COMplexes (ISCOMs(R)). Induction of multiple protective CTL responses by these polytope-ISCOM formulations were comparable to viral vector or DNA based delivery modalities as assessed by IFNgamma ELISpot, chromium release and viral challenge assays. Measurement of CTL responses specific for the different epitopes revealed immunodominance patterns, which were largely independent of the vaccine vector or the order of the epitopes in the polytope. ISCOMs thus emerge as a viable human delivery modality for protein-based polytope vaccines.

Amino Acid Sequence↗
PubMed2001

Intranasal immunisation with influenza-ISCOM induces strong mucosal as well as systemic antibody and cytotoxic T-lymphocyte responses.

Intranasal administration of vaccines is preferred for induction of mucosal immune responses. In this study, mice were immunised intranasally and subcutaneously with influenza-immuno stimulating complexes (influenza-ISCOM). The intranasal dose was 15-times the subcutaneous dose. All mice dosed with influenza-ISCOMs survived challenge with live virus and comparable serum antibody and splenic cytotoxic T-lymphocyte responses were detected in both groups. Induction of mucosal IgA was significantly higher with intranasal immunisation and was comparable to responses induced with the heat labile enterotoxin of Escherichia coli as adjuvant. These findings demonstrate that intranasal administration of high dose influenza-ISCOM results in potent systemic and mucosal immune responses.

Adjuvants, Immunologic↗
PubMed2001

Immune responses to ISCOM formulations in animal and primate models.

ISCOMs are typically 40 nm cage-like structures comprising antigen, saponin, cholesterol and phospholipid. ISCOMs have been shown to induce antibody responses and activate T helper cells and cytolytic T lymphocytes in a number of animal species, including non-human primates. Recent clinical studies have demonstrated that ISCOMs are also able to induce antibody and cellular immune responses in humans. This review describes the current understanding of the ability of ISCOMs to induce immune responses and the mechanisms underlying this property. Recent progress in the characterisation and manufacture of ISCOMs will also be discussed.

Animals↗
PubMed2001

Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine.

Current therapies for the treatment of hepatitis C virus (HCV) infection are only effective in a restricted number of patients. Cellular immune responses, particularly those mediated by CD8(+) CTLs, are thought to play a role in the control of infection and the response to antiviral therapies. Because the Core protein is the most conserved HCV protein among genotypes, we evaluated the ability of a Core prototype vaccine to prime cellular immune responses in rhesus macaques. Since there are serious concerns about using a genetic vaccine encoding for Core, this vaccine was a nonclassical ISCOM formulation in which the Core protein was adsorbed onto (not entrapped within) the ISCOMATRIX, resulting in approximately 1-microm particulates (as opposed to 40 nm for classical ISCOM formulations). We report that this Core-ISCOM prototype vaccine primed strong CD4(+) and CD8(+) T cell responses. Using intracellular staining for cytokines, we show that in immunized animals 0.30-0.71 and 0.32-2.21% of the circulating CD8(+) and CD4(+) T cells, respectively, were specific for naturally processed HCV Core peptides. Furthermore, this vaccine elicited a Th0-type response and induced a high titer of Abs against Core and long-lived cellular immune responses. Finally, we provide evidence that Core-ISCOM could serve as an adjuvant for the HCV envelope protein E1E2. Thus, these data provide evidence that Core-ISCOM is effective at inducing cellular and humoral immune responses in nonhuman primates.

Adjuvants, Immunologic↗
PubMed2000

Induction of lymphocyte recruitment in the absence of a detectable immune response.

Lymphocyte recruitment from blood into the lymph node is thought to be initiated by the presence of antigen. In this study, we have used lymphatic cannulation in sheep to demonstrate that the adjuvant ISCOMATRIX can induce dramatic lymph node activation in the absence of antigen. Consistent patterns of node shutdown (decreased output) and cell recruitment (increased output) with minimal blast cell responses were observed indicating that an antigen-specific immune response is not required. Production of IL-6, IL-8 and IFN-gamma, and the transient presence of red blood cells and neutrophils in the efferent lymph were associated with changes in efferent lymph cell trafficking. These early events may facilitate the screening of low frequency antigen-specific cells for binding to antigen and the subsequent amplification of the immune response.

Adjuvants, Immunologic↗
PubMed2000

Service utilization following traumatic brain injury.

OBJECTIVES: To document service utilization by people with a traumatic brain injury at different times postinjury and to identify factors that predict service use. DESIGN: Cross-sectional study design. Four groups of subjects were randomly selected from a regional database, according to their time postinjury: 6-18 months; 2-4 years; 6-9 years; and 10-17 years. SUBJECTS: A total of 119 adults with a traumatic brain injury (TBI). SETTING: Hospital and community-based clients in Sydney, Australia. OUTCOME MEASURES: Glasgow Outcome Scale, Disability Rating Scale; Functional Independence Measure; Lidcombe Psychosocial Disability Scale; number, type, and frequency of services used in the previous 12 months. RESULTS: Subjects in all four groups used a variety of services. The mean number of services used was 4.2, and there was only a moderate decline in service use over time. The use of medical and allied health services remained high in all four groups. Severity of injury, physical and cognitive disability, and psychosocial disability were all predictors of service utilization. Psychosocial disability was strongly associated with ongoing service utilization. CONCLUSION: In this study, people with TBI used services well beyond the early stage of recovery. Psychosocial disability may be a better predictor of service use than physical and cognitive disability alone.

Activities of Daily Living↗
PubMed1998

Studies on experimental adjuvanted influenza vaccines: comparison of immune stimulating complexes (Iscoms) and oil-in-water vaccines.

Detergent-disrupted influenza virus vaccines, formulated as Iscoms, or oil-in-water (o/w) emulsions, were administered parenterally to mice and evaluated for immunogenicity and protective efficacy. Both formulations enhanced both primary and secondary serum antibody responses. The magnitude of these responses with o/w emulsions was further enhanced by the addition of the non-ionic block copolymer L121 in the emulsion. Four weeks after primary immunization, mice were challenged by exposure to an aerosol containing infectious virus. Resistance to challenge in terms of survival rate and weight change correlated well with serum antibody titre for all formulations. Two major differences were observed between the adjuvant formulations. Iscom vaccines, formulated with Quil-A or the less toxic Quillaia saponin preparation Iscoprep 703, induced specific cytotoxic T-lymphocyte responses, whereas the o/w-based vaccines did not. In addition, dose-site reactivity studies in sheep showed that Iscom vaccines were less reactive than o/w-based vaccines, the degree of reactivity of the latter increasing sharply with increasing L121 concentration. On the basis of these studies, Iscoms were chosen for development as a potential adjuvant for human influenza vaccines.

Adjuvants, Immunologic↗
PubMed1997

The association between external weather conditions and pain and stiffness in women with rheumatoid arthritis.

OBJECTIVE: To determine the self-reported prevalence of weather sensitivity in a sample of female patients with rheumatoid arthritis (RA), and to determine if there is objective evidence of associations between weather and pain and stiffness in female patients with RA. METHODS: Fifty-three female patients residing in the Sydney metropolitan area participated in a study on the psychological determinants of disability from 1985 to 1987. During the study, subjects recorded pain on a visual analog scale and duration of morning stiffness for 14 day periods at 3-4 monthly intervals over 1-3 years (X = 15.7 months). After completion of the study, data on weather conditions were collected from the Bureau of Meteorology for the days that pain and stiffness records were made. Descriptive statistics and autoregression were used to analyze the data. RESULTS: Sixty percent of subjects reported that they were sensitive to weather. Six weather variables made a statistically significant contribution to daily pain score (p < 0.0001). However, they accounted for only 2.5% of the variance. Two weather variables contributed to duration of morning stiffness (p < 0.0001), but again these variables accounted for only a small portion of the variance (1.1%). A separate analysis for pain was carried out on the data from subjects who reported being weather sensitive. The results were consistent with those of the other analyses, with 2 variables accounting for only 1.7% of the variance (p < 0.0001). CONCLUSION: On the basis of these results it appears that weather makes only a minimal contribution to pain and stiffness in women with RA. The study may have been limited by its use of static measures of weather variables and pain. Further research using dynamic measures of pain and weather and a more extensive range of weather variables is needed.

Arthritis, Rheumatoid↗
PubMed1994

Negative staining can cause clumping of Bordetella pertussis fimbriae.

The state of fimbriae type 2 (Fim 2) and fimbriae type 3 (Fim 3) preparations from Bordetella pertussis were examined by negative stain electron microscopy. Uranyl acetate induced clumping of Fim 3 regardless of pH and was unsuitable as a stain for establishing the state of fimbriae. Both ammonium molybdate and sodium phosphotungstate were able to show the differences in Fim 3 stored at pH 7.2 and pH 9.5.

Antibodies, Bacterial↗
PubMed1990

Unions.

Dealing with a union is not complicated. If you are a member of the union, take that membership seriously and exercise your rights and responsibilities. Know what your contract says and live by it. If you disagree with what you are told to do by your supervisor, do it and grieve later. If you are a manager, know your contract and always keep it handy for reference. When you are unsure of the answer, get help from your labour relations advisor. Treat discipline as a process for helping an employee to perform the way you want them to perform. If you were a good manager before you became unionized, you can probably just continue on as you were before and you won't have any serious problems. For both management and non-management employees, remember that both of you have a job to do. Those jobs should be compatible. When you get to know your union, you will learn that they really are.

Canada↗