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Successful Vaccination (successful + vaccination)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Freeze-and-thaw-disrupted tumour cells impair the responsiveness of DC to TLR stimulation

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2008
Iñigo Tirapu
Abstract Cancer immunotherapy aims at inducing immune responses against tumour-associated antigens that mediate the eradication of tumour cells. For successful vaccination against antigens expressed by the tumour, the immune system has to be provided with sufficient amounts of these antigens in connection with strong immunostimulatory signals such as toll-like receptor (TLR) ligands. Tumour cells represent a convenient source of relevant tumour-associated antigens but can have suppressive properties. In this study, we explored how different forms of tumour cell material influence the activation of dendritic cells (DC), which play a crucial role in the induction of anti-tumour immune responses. We show that freeze-and-thaw-disrupted tumour cells inhibit DC activation in response to TLR stimulation, a phenomenon that is only partially seen with non-disrupted control cells. This suppression of DC stimulation is independent of tumour cell- and species-specific factors. We tested the hypothesis that phosphatidylserine on cells with disrupted membrane integrity mediates inhibition of TLR-induced DC activation. Our experimental evidence indicates that phosphatidylserine is not involved in the inhibition of TLR-mediated DC activation by freeze-and-thaw-disrupted cells. The inhibitory activity associated with disrupted tumour cells could explain why such preparations are less effective tumour vaccines than apoptotic tumour cells. [source]

Vaccination against hepatitis B in liver transplant recipients: Pilot analysis of cellular immune response shows evidence of HBsAg-specific regulatory T cells

LIVER TRANSPLANTATION, Issue 3 2007
Tanja Bauer
After liver transplantation for hepatitis-B-related diseases, patients currently receive lifelong treatment with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine have failed. A recent study with a new adjuvanted hepatitis B vaccine was exceptionally successful, leading to a high-titered long-lasting antibody response in 80% of all vaccinees. To identify the immunological mechanisms behind these unexpected results, the successfully vaccinated participants were tested for hepatitis B surface antigen (HBsAg)-specific T and B cells, and their cellular responses to revaccination with conventional vaccine were studied. HBsAg-specific CD4+ T lymphocytes could be detected in 13 of 16 patients after immunization with the new vaccine. Unexpectedly, these T cells produced almost exclusively interleukin (IL)-10 and had a CD4+/CD25+ phenotype. They were functionally active, suppressing cytokine secretion in HBsAg-specific (Th1) cells, thus representing antigen-specific regulatory T cells (TReg). Following a booster dose with conventional vaccine 22-31 months after completion of the initial vaccination series, the T-cell pattern in the revaccinated individuals changed substantially: 7 days after revaccination 9 of 11 individuals showed a switch to a Th1-type immune response with HBsAg-specific T cells secreting IL-2, interferon gamma and tumor necrosis factor alpha as observed in healthy controls. Four weeks after the booster, 4 patients still showed a Th1-type cytokine pattern, whereas in 5 patients only IL-10-secreting cells were detectable. After 1 year, in 3 of 4 revaccinated individuals only IL-10-secreting cells could be found, whereas the specific T cells of the fourth patient still showed a Th1-type of response. HBsAg-specific TReg cells could be demonstrated in HBV-positive liver transplant recipients successfully immunized with a new adjuvanted vaccine. Revaccination led to immediate disappearance of the these cells and the appearance of HBsAg-specific T cells with a Th1-type cytokine profile, which in most cases were replaced by the IL-10-secreting regulatory cells during the following months. The specific induction of TReg cells could contribute to the poor response of liver transplant recipients to conventional vaccine. In conclusion,, for successful vaccination of these patients, a vaccine with a strong inhibitory effect on TReg cells would be desirable. Liver Transpl 13:434,442, 2007. © 2007 AASLD. [source]

The development of artemisinin resistance in malaria: reasons and solutions

PHYTOTHERAPY RESEARCH, Issue 7 2010
Cosima Chrubasik
Abstract Despite world-wide efforts in fighting malaria, this mosquito-borne infectious disease is a huge burden for the population, especially in tropical and subtropical areas. The WHO recommends artemisinin-based combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria. However, artemisinin resistance cannot now be ignored. Factors affecting the development of artemisinin resistance include uncontrolled use of artemisinin-based combination therapy (ACT), mobile populations and migrants, artemisinin monotherapy, the use of subtherapeutic levels of artesiminin, substandard and counterfeit drugs, high treatment cost, and co-use of artemisinin derivates as prophylactic agents. Promising herbal alternatives are already in the pipeline, but the only long-term solution for eradicating malaria would be the development of a successful vaccination. Copyright © 2010 John Wiley & Sons, Ltd. [source]

An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer : The GC4 study

CANCER, Issue 9 2006
Jaffer A. Ajani M.D.
Abstract BACKGROUND Gastrin hormone is trophic to in vitro gastric cancer, and the antigastrin antibodies (AGAs) are antiproliferative and antimetastatic. Human gastric cancers overexpress gastrin genes and receptors that react to gastrin's trophic effects. Immunogen G17DT elicits a specific and high-affinity AGA. The authors evaluated G17DT vaccination given with cisplatin plus 5-fluorouracil for the treatment gastric adenocarcinoma. METHODS In this multicenter, Phase II study, patients received G17DT vaccination intramuscularly on Weeks 1, 5, 9 and 25 and cisplatin plus 5-fluorouracil every 28 days. Eligible patients had untreated, metastatic, or unresectable gastric or gastroesophageal adenocarcinoma with near-normal organ function. The primary endpoint of the study was the over response rate (ORR), and secondary endpoints included overall survival (OS), safety, and the impact of successful vaccination on patient outcome. RESULTS In total, 103 patients were enrolled in 5 countries. Seven patients who were overdosed inadvertently with 5-fluorouracil (a major protocol violation) were removed from the analysis. The confirmed ORR was 30% in 79 patients who were evaluated for response. The median time-to-progression (TTP) was 5.4 months, and the median survival (MS) was 9.0 months (n = 96 patients). Sixty-five of 94 patients who were vaccinated (69%) had 2 consecutive AGA titers of ,1 units (successfully vaccinated patients or immune-responders). The TTP was longer in immune-responders than in immune-nonresponders (P = .0005). Similarly, the MS was longer in immune-responders than in immune-nonresponders (10.3 months vs. 3.8 months; P ,.0001). In a multivariate analysis, successful vaccination was an independent OS prognosticator (P = .0001). G17DT did not have an adverse effect on safety. CONCLUSIONS The results demonstrated that successful G17DT vaccination was correlated with longer TTP and MS. AGA response was an independent OS prognosticator. A Phase III evaluation of G17DT in gastric cancer is warranted. Cancer 2006. © 2006 American Cancer Society. [source]