40 research outputs found
P16-45. High avidity CD4+ T cell response directed to an immunodominant Gag epitope in HIV controllers: an ANRS EP36 study
International audiencen.
Human Macrophages and Dendritic Cells Can Equally Present MART-1 Antigen to CD8+ T Cells after Phagocytosis of Gamma-Irradiated Melanoma Cells
Dendritic cells (DC) can achieve cross-presentation of naturally-occurring
tumor-associated antigens after phagocytosis and processing of dying tumor
cells. They have been used in different clinical settings to vaccinate cancer
patients. We have previously used gamma-irradiated MART-1 expressing melanoma
cells as a source of antigens to vaccinate melanoma patients by injecting
irradiated cells with BCG and GM-CSF or to load immature DC and use them as
a vaccine. Other clinical trials have used IFN-gamma activated macrophage
killer cells (MAK) to treat cancer patients. However, the clinical use of
MAK has been based on their direct tumoricidal activity rather than on their
ability to act as antigen-presenting cells to stimulate an adaptive antitumor
response. Thus, in the present work, we compared the fate of MART-1 after
phagocytosis of gamma-irradiated cells by clinical grade DC or MAK as well
as the ability of these cells to cross present MART-1 to CD8+
T cells. Using a high affinity antibody against MART-1, 2A9, which specifically
stains melanoma tumors, melanoma cell lines and normal melanocytes, the expression
level of MART-1 in melanoma cell lines could be related to their ability to
stimulate IFN-gamma production by a MART-1 specific HLA-A*0201-restricted
CD8+ T cell clone. Confocal microscopy with Alexa FluorÂź647-labelled
2A9 also showed that MART-1 could be detected in tumor cells attached and/or
fused to phagocytes and even inside these cells as early as 1 h and up to
24 h or 48 h after initiation of co-cultures between gamma-irradiated melanoma
cells and MAK or DC, respectively. Interestingly, MART-1 was cross-presented
to MART-1 specific T cells by both MAK and DC co-cultured with melanoma gamma-irradiated
cells for different time-points. Thus, naturally occurring MART-1 melanoma
antigen can be taken-up from dying melanoma cells into DC or MAK and both
cell types can induce specific CD8+ T cell cross-presentation
thereafter
IL-12 and GM-CSF in DNA/MVA Immunizations against HIV-1 CRF12_BF Nef Induced T-Cell Responses With an Enhanced Magnitude, Breadth and Quality
In Argentina, the HIV epidemic is characterized by the co-circulation of subtype B and BF recombinant viral variants. Nef is an HIV protein highly variable among subtypes, making it a good tool to study the impact of HIV variability in the vaccine design setting. We have previously reported a specific cellular response against NefBF with low cross-reactivity to NefB in mice. The aim of this work was to analyze whether the co-administration of IL-12 and GM-CSF, using DNA and MVA vaccine vectors, could improve the final cellular response induced. Mice received three DNA priming doses of a plasmid that express NefBF plus DNAs expressing IL-12 and/or GM-CSF. Afterwards, all the groups were boosted with a MVAnefBF dose. The highest increase in the magnitude of the NefBF response, compared to that induced in the control was found in the IL-12 group. Importantly, a response with higher breadth was detected in groups which received IL-12 or GM-CSF, evidenced as an increased frequency of recognition of homologous (BF) and heterologous (B) Nef peptides, as well as a higher number of other Nef peptide pools representing different viral subtypes. However, these improvements were lost when both DNA cytokines were simultaneously administered, as the response was focused against the immunodominant peptide with a detrimental response towards subdominant epitopes. The pattern of cytokines secreted and the specific-T-cell proliferative capacity were improved in IL-12 and IL-12+GM-CSF groups. Importantly IL-12 generated a significant higher T-cell avidity against a B heterologous peptide
T-Cell Immune Responses Against Env from CRF12_BF and Subtype B HIV-1 Show High Clade-Specificity that Can Be Overridden by Multiclade Immunizations
BACKGROUND: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections caused by subtype B and BF variants. The aim of this study was to characterize in mice the immunogenic and antigenic properties of the Env protein from CRF12_BF in comparison with clade B, employing prime-boost schemes with the combination of recombinant DNA and vaccinia virus (VV) vectors. METHODOLOGY/PRINCIPAL FINDINGS: As determined by ELISPOT from splenocytes of animals immunized with either EnvBF or EnvB antigens, the majority of the cellular responses to Env were found to be clade-specific. A detailed peptide mapping of the responses reveal that when there is cross-reactivity, there are no amino acid changes in the peptide sequence or were minimal and located at the peptide ends. In those cases, analysis of T cell polifunctionality and affinity indicated no differences with respect to the cellular responses found against the original homologous sequence. Significantly, application of a mixed immunization combining both clades (B and BF) induced a broader cellular response, in which the majority of the peptides targeted after the single clade vaccinations generated a positive response. In this group we could also find significant cellular and humoral responses against the whole gp120 protein from subtype B. CONCLUSIONS/SIGNIFICANCE: This work has characterized for the first time the immunogenic peptides of certain EnvBF regions, involved in T cell responses. It provides evidence that to improve immune responses to HIV there is a need to combine Env antigens from different clades, highlighting the convenience of the inclusion of BF antigens in future vaccines for geographic regions where these HIV variants circulate
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Track A Basic Science
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd
The use of rituximab to prevent severe delayed haemolytic transfusion reaction in immunized patients with sickle cell disease
International audienceBackground: Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD).Study design: We report an observational study of eight alloimmunized SCD patients with history of severe DHTR who were treated with rituximab before a new transfusion to prevent further immunization and DHTR.Results: Five patients showed a good clinical outcome following transfusion preceded by preemptive treatment with rituximab. The remaining patients presented mild DHTR. In all patients, the results of post-transfusion screening tests were identical to those of pretransfusion tests; no newly formed antibodies were detected.Conclusion: These cases suggest that rituximab prevents at least occurrence of newly formed antibodies in high responders and minimizes the risk of severe DHTR. This study confirms that DHTR is complex in SCD and does not rely only on the classical antigens/antibodies conflict. Considering potentially serious adverse effect of rituximab, this treatment should be considered cautiously, and only when transfusion is absolutely necessary in patients with history of severe DHTR linked to immunization