ILD-specific health-related quality of life in systemic sclerosis-associated ILD compared with IPF.

Introduction: Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) are fibrotic ILDs with divergent disease populations. Little is known about health-related quality of life (HRQL) in SSc-ILD relative to IPF.

Methods: We used the Kings Brief Interstitial Lung Disease Questionnaire (K-BILD) to compare HRQL in a cross-sectional study of 57 patients with IPF and 29 patients with SSc-ILD.

A novel peptide-based vaccine candidate with protective efficacy against influenza A in a mouse model.

Current influenza vaccines mainly induce antibody responses to the variable hemagglutinin proteins of the virus strains included in the vaccine. Instead, a broadly protective influenza vaccine should aim at inducing antibody- and/or cell-mediated immunity against conserved viral proteins. Vacc-FLU is a peptide based vaccine combining conserved B and T cell epitopes.

Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

Background: In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24 vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI.

Methods: All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40.

Correlation of Antibody Responses to a Peptide Antigen gp120-C5/gp41 with HIV Disease Progression.

Antibodies to the carboxy-terminal constant (C5) region 5 of the HIV-1 envelope glycoprotein gp120 have previously been associated with slow disease progression. This is one of the regions on gp120 that interact with the transmembrane glycoprotein, gp41, anchoring it to the viral and infected cell membrane. This study analyzed humoral responses to a novel heterodimeric peptide construct comprising the C5 region and a compatible region on gp41.

Effect of the Modification of p24 Peptide Antigen on Dendritic Cell Uptake and T Cell Activation.

Background: Vacc-4x is a candidate therapeutic vaccine consisting of 4 modified peptides based on conserved regions of HIV-1 p24Gag. Vacc4x has been shown to induce long term cellular immunity in immunized infected individuals resulting a reduction in viral load on treatment interruption.

Objective: Vacc-4x peptides are modified.

A case for preART-adjusted endpoints in HIV therapeutic vaccine trials.

Background: In a randomized, double-blind, placebo-controlled phase 2 clinical trial of Vacc-4x, a peptide-based therapeutic HIV-1 p24(Gag) vaccine candidate, 135 HIV-infected participants (vaccine:placebo=92:43) received a series of six immunizations while on combination antiretroviral therapy (cART). At week 28, all participants underwent an analytical treatment interruption (ATI) for up to 24 weeks. preART VL appeared to be higher among Vacc-4x recipients.

Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial.

Background: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adults infected with HIV-1.

Expression of ESE-3 isoforms in immunogenic and tolerogenic human monocyte-derived dendritic cells.

Dendritic cells (DC) are the only hematopoietic cells expressing the epithelial specific Ets transcription factor ESE-3. Here we analyzed presence and quantity of isoforms ESE-3a, ESE-3b and ESE-3j in various immunogenic and tolerogenic human monocyte-derived DC (moDC) and blood DC populations using quantitative real time PCR and immunoblot analyses. ESE-3a and ESE-3b were detectable in all moDC populations with ESE-3b being the main transcript.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production.

Maturation of monocyte derived dendritic cells with OK432 boosts IL-12p70 secretion and conveys strong T-cell responses.

Background: Design of tumour specific immunotherapies using the patients' own dendritic cells (DC) is a fast advancing scientific field. The functional qualities of the DC generated in vitro are critical, and today's gold standard for maturation is a cytokine cocktail consisting of IL-1β, IL-6, TNF-α and PGE2 generating cells lacking IL-12p70 production. OK432 is an immunotherapeutic agent derived from killed Streptococcus pyogenes that has been used clinically to treat malignant and benign neoplasms for decades.

Levels of dendritic cell populations and regulatory T cells vary significantly between two commonly used mouse strains.

Dendritic cells (DC) are a heterogeneous group of professional antigen-presenting cells (APC) involved in both initiating immune responses and maintaining tolerance. Roughly, DC can be divided into plasmacytoid DC (pDC) and conventional DC (cDC). By controlling regulatory T cells (Treg), DC can influence the outcome of both immunity and autoimmunity.

A pilot study of the immune response to whole inactivated avian influenza H7N1 virus vaccine in mice.

Background: Highly pathogenic avian influenza (HPAI) outbreaks in domestic poultry bring humans into close contact with new influenza subtypes and represent a threat to human health. In 1999, an HPAI outbreak of H7N1 virus occurred in domestic poultry in Italy, and a wild-type virus isolate from this outbreak was chosen as a pandemic vaccine candidate.

Objectives: We conducted a pilot study to investigate the kinetics of the humoral immune response induced after immunisation with an egg grown whole inactivated H7N1 virus vaccine in BALB/c mice.

Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients.

Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record.

The humoral immune response and protective efficacy of vaccination with inactivated split and whole influenza virus vaccines in BALB/c mice.

Recently the urgency of developing a pandemic influenza vaccine has lead to the re-evaluation of the use of whole virus vaccine. We have compared the humoral immune response and the protective efficacy of whole and split influenza virus vaccines in mice. Whole virus vaccine was more immunogenic particularly after the first dose of vaccine, generally eliciting higher numbers of systemic antibody secreting cells and an earlier and higher neutralising antibody response.

The influence of CD4 and CXCR4 on maedi-visna virus-induced syncytium formation.

CD4 is the principal binding site for human and simian immunodeficiency virus (HIV/SIV) receptor interactions and the a chemokine receptor CXCR4 has been implicated as a primordial lentivirus receptor. This study sought to determine the relevance of CD4 and CXCR4 in virus-receptor interactions for the prototype lentivirus, maedi-visna virus (MVV) of sheep. Neither CD4 nor alpha/beta chemokine receptors represent principal receptors for MVV since human osteosarcoma cells devoid of these molecules were susceptible to productive infection.