Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen recognized by T cells-1.

PURPOSE: As compared with natural tumor peptide sequences, carefully selected analog peptides may be more immunogenic and thus better suited for vaccination. However, T cells in vivo activated by such altered analog peptides may not necessarily be tumor specific because sequence and structure of peptide analogs differ from corresponding natural peptides. EXPERIMENTAL DESIGN: Three melanoma patients were immunized with a Melan-A peptide analog that binds more strongly to HLA-A*0201 and is more immunogenic than the natural sequence. This peptide was injected together with a saponin-based adjuvant, followed by surgical removal of lymph node(s) draining the site of vaccination. RESULTS: Ex vivo analysis of vaccine site draining lymph nodes revealed antigen-specific CD8+ T cells, which had differentiated to memory cells. In vitro, these cells showed accelerated proliferation upon peptide stimulation. Nearly all (16 of 17) of Melan-A-specific CD8+ T-cell clones generated from these lymph nodes efficiently killed melanoma cells. CONCLUSIONS: Patient immunization with the analog peptide leads to in vivo activation of T cells that were specific for the natural tumor antigen, demonstrating the usefulness of the analog peptide for melanoma immunotherapy.

Preventing contagion with avian influenza: Disease salience, attitudes toward foreigners, and avoidance beliefs

Building on an evolutionary approach to outgroup avoidance, this study shows relations between perceived disease salience and beliefs in the efficacy of avoiding foreigners as protective measures, in the context of a real-life pandemic risk; i.e., avian influenza. People for whom avian influenza was salient and who held unfavourable attitudes toward foreigners were more likely to believe that avoiding contact with foreigners protects against infection. This finding suggests that individual differences in social attitudes moderate evolved mechanisms relating threat of disease to outgroup avoidance.

Development and validation of a clinical decision rule for the diagnosis of influenza.

INTRODUCTION: A clinical decision rule to improve the accuracy of a diagnosis of influenza could help clinicians avoid unnecessary use of diagnostic tests and treatments. Our objective was to develop and validate a simple clinical decision rule for diagnosis of influenza. METHODS: We combined data from 2 studies of influenza diagnosis in adult outpatients with suspected influenza: one set in California and one in Switzerland. Patients in both studies underwent a structured history and physical examination and had a reference standard test for influenza (polymerase chain reaction or culture). We randomly divided the dataset into derivation and validation groups and then evaluated simple heuristics and decision rules from previous studies and 3 rules based on our own multivariate analysis. Cutpoints for stratification of risk groups in each model were determined using the derivation group before evaluating them in the validation group. For each decision rule, the positive predictive value and likelihood ratio for influenza in low-, moderate-, and high-risk groups, and the percentage of patients allocated to each risk group, were reported. RESULTS: The simple heuristics (fever and cough; fever, cough, and acute onset) were helpful when positive but not when negative. The most useful and accurate clinical rule assigned 2 points for fever plus cough, 2 points for myalgias, and 1 point each for duration <48 hours and chills or sweats. The risk of influenza was 8% for 0 to 2 points, 30% for 3 points, and 59% for 4 to 6 points; the rule performed similarly in derivation and validation groups. Approximately two-thirds of patients fell into the low- or high-risk group and would not require further diagnostic testing. CONCLUSION: A simple, valid clinical rule can be used to guide point-of-care testing and empiric therapy for patients with suspected influenza.

Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen.

OBJECTIVE: To investigate the merits of vaccination against hepatitis B virus (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core antigen (anti-HBc). METHODS: HIV-positive patients with isolated anti-HBc and CD4 counts >200 cells/mm(3) received HBV vaccination. An antibody titre to hepatitis B surface antigen (anti-HBs titres) ≥10 IU/L one month post-vaccination was termed an anamnestic response; a titre <10 IU/L was termed a primary response. Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres in all responders were measured 12 and 24 months post-vaccination. RESULTS: 37 patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4 count was 443 cells/mm(3). 8/37 patients (22%) elicited an anamnestic response. 29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course, 15/25 primary responders (60%) achieved anti-HBs titres ≥10 IU/L. HIV acquisition through injecting drug use was the only independent predictor of an anamnestic response (OR 22.9, CI 1.71-306.74, P=0.018). Median anti-HBs titres for anamnestic and primary responders were 51 IU/L (13-127) and 157 IU/L (25-650) respectively. Of all responders, 12/23 (52%) retained anti-HBs titres ≥10 IU/L at 24 months. Anti-HBs duration was not significantly different between anamnestic and primary responders. CONCLUSIONS: 23/37 HIV-positive patients (62%) with isolated anti-HBc achieved anti-HBs titres ≥10 IU/L after 1-3 vaccine doses. However, duration of this immune response was short-lived (

RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.

The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8(+) T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8(+)/HLA-A2/RHAMM R3 tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells in accordance with an increase of R3-specific CD8(+) T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37.

Novel Influenza A (H1N1) Fact Sheet, 2009

The novel flu virus, that is currently circulating in the U.S. and other parts of the world, is a unique combination of swine and human flu viruses. This virus is transmitted from person to person, not from pigs to humans. None of the current cases had exposure to swine.

General Use of Face-Masks and Respirators to Prevent Novel Influenza A (H1N1, May 1, 2009

During this outbreak of swine influenza, many people have questions regarding the best way to protect themselves from becoming ill with the virus and, if you are ill, how to prevent spread of the disease to others.

Novel Influenza A (H1N1) Fact Sheet: General Public, May 1, 2009

What is novel influenza? The novel flu virus, that is currently circulating in the U.S. and other parts of the world, is a unique combination of swine and human flu viruses. This virus is transmitted from person to person, not from pigs to humans. None of the current cases had exposure to swine.

Influenza and Other Respiratory Virus Weekly Activity Report, May 16, 2009 Week 19

The Iowa Influenza Surveillance Network (IISN) is comprised of physicians, schools, child care centers, businesses, and long term care facilities who track the occurrence on influenza-like illness. In addition, the state influenza coordinator tracks the number of deaths due to pneumonia and influenza in Des Moines weekly as part of the 122-Cities Morbidity and Mortality reporting system sponsored by CDC.

Influenza and Other Respiratory Virus Weekly Activity Report, May 9, 2009 Week 18

The Iowa Influenza Surveillance Network (IISN) is comprised of physicians, schools, child care centers, businesses, and long term care facilities who track the occurrence on influenza-like illness. In addition, the state influenza coordinator tracks the number of deaths due to pneumonia and influenza in Des Moines weekly as part of the 122-Cities Morbidity and Mortality reporting system sponsored by CDC.

Influenza and Other Respiratory Virus Weekly Activity Report, May 2, 2009 Week 17

Weekly report of the Iowa Influenza Surveillance Network produced by the Iowa Department of Public Health.

Influenza and Other Respiratory Virus Weekly Activity Report, April 25, 2009, Week 16

Weekly report of the Iowa Influenza Surveillance Network produced by the Iowa Department of Public Health.

Influenza and Other Respiratory Virus Weekly Activity Report, April 18, 2009, Week 15

Weekly report of the Iowa Influenza Surveillance Network produced by the Iowa Department of Public Health.

Influenza and Other Respiratory Virus Weekly Activity Report, April 11, 2009, Week 14

Weekly report of the Iowa Influenza Surveillance Network produced by the Iowa Department of Public Health.

Influenza and Other Respiratory Virus Weekly Activity Report, April 4, 2009, Week 13

Weekly report of the Iowa Influenza Surveillance Network produced by the Iowa Department of Public Health.