flu
Maximizing influenza immunization in Edmonton: a collaborative model.

Sadoway DT, Loucraft JR, Johnston BA.

In 1991 the Edmonton Board of Health (EBH) entered into a partnership with seven senior citizen recreation centres to improve the efficiency of influenza immunization delivery by public health nurses in Edmonton. This initiative was driven by an annual increase in demand for flu vaccine coupled with diminishing health unit resources and a desire to collaborate with key community groups. A pilot project established that a cooperative approach could be more efficient than the previous health centre appointment model. In October 1991, 13,633 individuals were immunized with the assistance of 202 volunteer seniors who contributed 1,700 hours of their time. Unit labour costs incurred by the EBH were reduced by 40%. This model of delivery resulted in earlier completion of the flu immunization program and forged strong community alliances between the Edmonton Board of Health and the staff and volunteers of the seniors' recreational centres.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8180925&dopt=Abstract flu, flu medicine, tamiflu



flu
Carrier-mediated uptake and presentation of a major histocompatibility complex class I-restricted peptide.

Brander C, Wyss-Coray T, Mauri D, Bettens F, Pichler WJ.

Institute of Clinical Immunology, Inselspital, Bern, Switzerland.

Antigenic peptides derived from endogenous or viral proteins can associate with class I or class II major histocompatibility complex (MHC) molecules, while exogenous antigens are endocytosed, processed intracellularly and presented on MHC class II molecules. Here we describe a method that allows the presentation of an MHC class I-restricted antigenic peptide on MHC class I molecules, although it was taken up from the outside. The HLA-A2-restricted influenza virus matrix protein-derived peptide (flu, 57-68) was used either in soluble form or coupled via an S-S bridge to transferrin (Tf-flu). Target cells were incubated with flu or Tf-flu and the effective antigen presentation was detected in a cytotoxicity assay using flu peptide-specific, HLA-A2-restricted CD8+ cytotoxic T lymphocytes. Sensitization of target cells with Tf-flu required 5 to 10 times higher molar concentrations of peptide compared to sensitization with soluble free peptide. The Tf-flu construct was taken up by the cells via the Tf receptor (CD71) as the binding of Tf-flu was blocked by an excess of Tf. In contrast to the flu peptide, cytotoxicity elicited by Tf-flu was blocked by brefeldin A but not by chloroquine nor inhibitors of intracellular reducing steps, like 1-buthionine-(s,r)-sulfoximine or n-ethylmaleimide. Presentation of the flu peptide derived from Tf-flu construct is not hindered in the mutant T2 cell line, which lacks genes coding for transporter proteins for antigenic peptides (TAP1/TAP2) and proteasomes subunits, suggesting that the processing pathway described in this report may involve TAP-independent steps.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8258336&dopt=Abstract flu, flu medicine, tamiflu



flu
Identification of T-cell epitopes: rapid isolation of class I-presented peptides from viable cells by mild acid elution.

Storkus WJ, Zeh HJ 3rd, Salter RD, Lotze MT.

Department of Surgery, University of Pittsburgh School of Medicine, PA 15261.

A novel method was developed to isolate immunogenic peptides (CD8+ T-cell epitopes) from class I complexes expressed at the cell surface of viable cells. Cells treated at pH 3.3 with citrate-phosphate buffer for periods as short as 15 s remained viable and became phenotypically class I deficient. Qualitative loss of class I determinants was verified both serologically and by the incapacity of acid-treated cells to be lysed by class I-restricted cytolytic T lymphocytes (CTLs) in contrast to non-acid-treated controls. Flow cytometric analysis of acid-treated cells suggests that class I heavy chains remain associated with the cell membrane, while the class I light chain (beta 2-microglobulin) is absent. Since the physical dissociation of beta 2-microglobulin from class I heavy chain is correlated with the release of previously class I-bound peptides, we examined acid-eluted cell-free supernatants for the presence of immunogenic peptides. Peptides were acid eluted from an influenza A strain-infected, HLA-A2+ cell line and were subsequently fractionated by reverse-phase high performance liquid chromatography (RP-HPLC). These fractionated peptides were examined for their capacity to sensitize an HLA-A2+ B cell line to lysis mediated by an influenza A matrix peptide- (Flu M1 57-68) specific, HLA-A2-restricted CTL line. A single peak of biologic activity was identified in HPLC fractions 47 and 48 derived from influenza-infected cells. These fractions contained a peptide of M(r) 968 with a sequence similar to the Flu M1 58-66 sequence GILGFVFTL. The application of this technique to other T-cell-based systems may aid in the definition of peptide epitopes relevant to viral, autoimmune, or neoplastic disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7506576&dopt=Abstract flu, flu medicine, tamiflu



flu
Skewing to the LFA-3 adhesion pathway by influenza infection of antigen-presenting cells.

van Kemenade FJ, Kuijpers KC, de Waal-Malefijt R, van Lier RA, Miedema F.

Dept. of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.

The effect of influenza (FLU) infection on heterotypic conjugate formation between antigen-presenting cells and T lymphocytes has been studied with FLU-specific T cell clones and FLU-infected B-lymphoblastoid cells (B-LCL). Conjugate formation between FLU-infected B-LCL (FLU+ B-LCL) and T cells was found to be consistently enhanced in comparison with peptide-sensitized or uninfected B-LCL. Treatment of B-LCL with exogenous neuraminidase (NA-NAse) similarly enhanced conjugate formation indicating that increased conjugate formation may be mediated by the viral neuraminidase. Monoclonal antibody blocking experiments revealed that the contribution by CD2/LFA-3 is increased relative to that of LFA-1/ICAM-1 in conjugates between FLU+ B-LCL or NANAse-treated B-LCL and T cell clones. In contrast, both pathways of adhesion contributed equally to conjugate formation between peptide-sensitized B-LCL or control B-LCL and T cell clones. Thus, FLU infection causes increased conjugate formation between antigen-presenting cells and T cells and skews towards CD2/LFA-3-dependent adhesion, independent of T cell receptor signalling.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7680612&dopt=Abstract flu, flu medicine, tamiflu



flu
Zanamivir (Relenza )--a new treatment for influenza.

MacConnachie AM.

Deaths from influenza are recorded every year in the UK and flu epidemics raise concerns for the safety of the young, the elderly and other vulnerable groups in the community. Not surprisingly, the launch of zanamavir (Relenza) by Glaxo Welcome (Middlesex, UK) has received much attention in the medical media and lay press. Just who should receive this treatment and under what conditions it should be given remains to be confirmed in practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11868584&dopt=Abstract flu, flu medicine, tamiflu



flu
Epidemiology of influenza vaccination in Canada.

Duclos P, Hatcher J.

Bureau of Communicable Disease Epidemiology, Laboratory Centre for Disease Control, Ottawa, ON.

To assess influenza vaccine coverage among Canadian adults, questions about the fall/winter 1990-91 immunization campaign were added to the Statistics Canada 1991 General Social Survey. A total of 11,924 usable responses were obtained (response rate 80%). Overall, an estimated 13.8% (95% CI 13.1-14.5) of the Canadian population surveyed and 44.8% (95% CI 42.7-46.9) of the population 65 years of age and over received a "flu" shot during the fall/winter 1990-91 immunization campaign. A logistic regression model run separately in populations less than 65 years of age and in populations 65 and over reveals that, by far, the major predictor for receiving influenza vaccine was a recommendation by a nurse or physician. Two major reasons listed by persons 65 and over for not receiving the flu vaccine were 1) the belief they hardly ever get the flu (39%), and 2) they fear side effects (22%).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8269378&dopt=Abstract flu, flu medicine, tamiflu