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At least 703 records · Page 39Linked to original sources
PubMed2000

Vaccine properties of antigens entrapped in microparticles produced by spray-drying technique and using various polyester polymers.

The present study investigated the suitability of various microparticles produced by spray-drying technique to entrap and preserve the physiochemical and biological properties of an antigen. These microparticles were constituted either by poly(lactide) polymers characterized by various molecular weight or poly(lactide-co-glycolide) polymers. The recombinant 28 kDa glutathione S-transferase of Schistosoma mansoni (rSm28GST) characterized by major epitopes involved in the active site of this enzyme was selected as model antigen. The microparticles were characterized by a mean size </=5 microm and an antigen loading of approximately 2% (w/w). The analysis by SDS-PAGE electrophoresis of the rSm28GST released from microparticles confirmed the conservation of its physicochemical characteristics. The conservation of the native structure of the entrapped antigen was confirmed by detecting its enzymatic activity after release from microparticles. A single intraperitoneal immunization of mice with rSm28GST entrapped in microparticles resulted in a specific antibody response, which remained high for at least 7 months. The analysis of the isotype profile indicated that immunized mice primarily produced anti-rSm28GST immunoglobulin (Ig) G1 with the coexistence of lower IgG2a and IgG2b levels. Finally, the recognition of the major epitopic regions and the neutralization of the enzymatic activity of the rSm28GST by the antisera confirmed the specificity of the response against the native structure of the antigen. These results confirmed the integrity of the entrapped antigen. Moreover, our results supported the hypothesis that the duration of antigen release is the limiting factor for the duration of antibody production. Indeed, the use of polymers characterized by different molecular weights allowed us to modify the duration of the immune response. Together, these results demonstrated that microencapsulation of an antigen by spray-drying preserved its crucial characteristics required to generate an effective humoral immune response after a single-dose administration.

Animals↗
PubMedDate not supplied

In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer--changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile.

In order to provoke an immune response, a tumor vaccine should not only maximize antigen-specific signals, but should also provide the necessary "co-stimulatory" environment. One approach is to genetically manipulate tumor cells to either secrete lymphokines (GM-CSF, IL-12, IL-15) or express membrane bound molecules (CD80, CD86). Furthermore, patient dendritic cells can be loaded with tumor-associated antigens or peptides derived from them and used for immunotherapy. Genetic modification of dendritic cells can also lead to presentation of tumor-associated antigens. Transfection of dendritic cells with DNA encoding for such antigens can be done in vitro, but transfection efficiency has been uniformly low. Alternatively, dendritic cells can also be modulated directly in vivo either by "naked" DNA immunization or by injecting replication-deficient viral vectors that carry the tumor specific DNA. Naked DNA immunization offers several potential advantages over viral mediated transduction. Among these are the inexpensive production and the inherent safety of plasmid vectors, as well as the lack of immune responses against the carrier. The use of viral vectors enhances the immunogenicity of the vaccine due to the adjuvant properties of some of the viral products. Recent studies have suggested that the best strategy for achieving an intense immune response may be priming with naked DNA followed by boosting with a viral vector. We have successfully completed a phase I and phase II clinical trials on immunotherapy of prostate cancer using naked DNA and adenoviral immunizations against the prostate-specific membrane antigen (PSMA) and phase I clinical trial on colorectal cancer using naked DNA immunization against the carcinoembryonic antigen (CEA). The vaccination was tolerated well and no side effects have been observed so far. The therapy has proven to be effective in a number of patients treated solely by immunizations. The success of the treatment clearly depends on the stage of the disease proving to be most efficient in patients with minimal disease or no metastases. A panel of changes in the phenotype of peripheral blood lymphocytes and the expression of intra-T-cell lymphokines seems to correlate with clinical improvement.

Adenoviridae↗
PubMed1999

Search for an antibody profile of Rhodococcus equi infection in AIDS patients despite the diversity of isolates and patient immune dysfunction.

Diversity of virulence-associated antigens of Rhodococcus equi was detected among thirteen strains isolated from AIDS patients on two continents. One out of four Brazilian isolates presented the virulence-associated antigen of 15- to 17-kDa, and the other three isolates had the 20-kDa virulence-associated antigen. In contrast, only three out of nine Italian isolates were positive for virulence-associated antigens - two for the 15- to 17-kDa antigen and one for the 20-kDa antigen. In four other Italian strains, one or more other low-molecular-weight antigens were identified. Because of R. equi variability and host immune dysfunction, no characteristic antibody profile was detected among patients, although the presence of specific antibodies in serum samples suggested prognostic value: good patient outcome and recovery from pneumonia were correlated with R. equi antibody detection, whereas the lack or disappearance of specific antibodies, mainly those to low-molecular-weight antigens, was correlated with disease progression and patient death. These results confirmed the nonobligatory presence of the well-known virulence-associated antigens for the pathogenicity of R. equi in humans, and also the diversity of R. equi strains isolated from AIDS patients, which may be related to the geographic origin of the isolates or may be a consequence of the route of R. equi transmission in different countries. Some mechanisms underlying the results obtained are discussed, suggesting immune complex formation during the progress of the disease.

AIDS-Related Opportunistic Infections↗
PubMed2026

H3K9ac promoter profiling and their association with gene expression in immune cells of T2-high asthma patients.

BACKGROUND: Asthma is a heterogeneous chronic inflammatory syndrome, with the T2-high endotype defined by robust type 2 immune responses and skewed T helper polarization. Although H3K9 acetylation (H3K9ac) is a key activating histone mark in T helper differentiation, its genome-wide promoter landscape in circulating immune cells of T2-high asthma remains uncharacterized. METHODS: Integrated ChIP-seq and RNA-seq profiling was performed on peripheral blood mononuclear cells (PBMCs) from ten T2-high asthma patients and ten healthy controls. Differential H3K9ac enrichment and gene expression were analyzed, followed by concordance and Spearman correlation analyses to identify genes under H3K9ac-linked transcriptional regulation. Findings were contextualized using publicly available H3K27ac ChIP-seq datasets from asthmatic airway tissue and glucocorticoid-treated airway epithelial cells. RESULTS: We identified 2340 differential enrichment regions (DERs), 95.9% mapping to promoters, with nearly all showing H3K9ac loss and enrichment in T cell receptor signaling and Th1/Th2/Th17 differentiation pathways. Genes encoding histone-modifying enzymes, including HATs, HDACs, and HMTs, were overrepresented, suggesting a self-reinforcing epigenetic feedback loop. Integrated analysis identified 979 genes with concordant H3K9ac and expression changes: downregulated genes were enriched in lymphocyte activation and TNF signaling, whereas upregulated genes were enriched in AKT and MAPK pathways. Locus-specific analyses showed H3K9ac loss at Th1/Th17 genes (TBX21, IFNG, CCR6) and gain at Th2 genes (IL4, TSLP). Targeted RT-qPCR provided independent experimental support for reduced expression of Th1-associated genes, with significant decreases in STAT1 and STAT4 in T2-high asthma patients. Correlation analysis identified six genes with significant H3K9ac-expression associations. CONCLUSIONS: Promoter H3K9ac remodeling is a defining epigenetic feature of T2-high asthma, reflecting coordinated alterations at T helper lineage-defining loci and inflammatory pathways.

Asthma↗
PubMed1988

Use of anti-M. leprae phenolic glycolipid-I antibody detection for early diagnosis and prognosis of leprosy.

Untreated patients suffering from tuberculoid, lepromatous and indeterminate leprosy, their domiciliary contacts, and healthy controls, all living in Guadeloupe, West Indies, were tested by an ELISA for detecting IgM antibodies to the terminal disaccharide of the phenolic glycolipid-I antigen of Mycobacterium leprae. On most subjects, a Mitsuda test was also performed. A large majority of the tuberculoid patients and healthy subjects were Mitsuda positive. The seropositivity rate reached 44% among tuberculoid patients, and 6% among healthy subjects, with low antibody levels. Lepromatous patients were all Mitsuda negative and seropositive, with antibody production varying from low levels, as seen in tuberculoid patients, to much higher levels. Indeterminate leprosy patients included 62% Mitsuda-positive subjects and 54% seropositive subjects with a large dispersion of antibody levels. Comparing the results of the Mitsuda test to those of the ELISA by factorial analysis allowed us to define several subgroups among this population: some (25%) showed a "lepromatous-like" immune status (Mitsuda negative, seropositive); others (54%) exhibited "tuberculoid-like" profiles (Mitsuda positive without antibodies or with low antibody levels). "Lepromatous-like" cases were significantly older than "tuberculoid-like" patients. A group of subjects (17%) was Mitsuda negative and seronegative, thus displaying a true "indeterminate" immune profile, which had not been seen in other forms of the disease and had been observed in only 2 out of 51 healthy controls. A large majority of contacts was Mitsuda positive, with 33% of them being seropositive, indicating that the prevalence of M. leprae infection greatly exceeds that of overt leprosy in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed2025

Construction and accuracy assessment of an efferocytosis-related prognostic model for ovarian cancer: A diagnostic accuracy study.

The study aimed to investigate the prognostic significance of efferocytosis-related genes in ovarian cancer (OC) with regard to cancer development, progression, invasion, and metastasis. OC cohorts were assembled from bioinformatics repositories. Utilizing consensus clustering analysis, distinct clusters were delineated based on the intersection of OC-related genes and efferocytosis-related genes. A prognostic signature specific to efferocytosis in OC was developed using data from The Cancer Genome Atlas, validated against the gene expression omnibus database, and subjected to independent prognostic analysis. Subsequently, a nomogram model was formulated. Moreover, investigations encompassed the immune microenvironment, immunotherapy, mutation profiling, drug sensitivity assessments, drug prediction models, and molecular docking analyses. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were employed to ascertain the mRNA expression levels of key genes. Five key genes, FCGBP, BTN3A3, WDR91, SLC25A45, and BTNL3, were identified as significantly associated with OC. Both datasets and qRT-PCR demonstrated elevated expression levels of FCGBP and WDR91 in OC. Notably, AFLATOXIN B1 exhibited strong binding affinity to SLC25A45, ciclopirox to BTN3A3, and irinotecan to WDR91. The risk score, age, and stage were identified as independent prognostic factors, with the nomogram displaying efficacy in predicting OC patient survival. Variations in the immune cell infiltration profiles, including naive B cells, and expression levels of 6 immune checkpoint genes, such as CTLA4, were notable. High tumor mutation burden scores were associated with improved survival outcomes. Additionally, significant differences in the IC50 values of 123 anticancer drugs were observed between the 2 risk groups. This findings of this study highlight the efficacy of the efferocytosis-associated risk model in predicting the survival outcomes of OC patients, thus providing a novel reference for prognostic prediction in OC patients.

Humans↗
PubMed1998

Lymphocyte T subset counts in children with hypercholesterolemia receiving dietary therapy.

BACKGROUND: In children with hypercholesterolemia, dietary therapy is indicated; however, we do not know if a low-fat diet can modify some organic functions, i.e. immune function. METHODS: 42 children with hypercholesterolemia received a low-fat, low-cholesterol diet during 6 months. At baseline and after the treatment period, we determined a lipoprotein profile and some immune characteristics: immunoglobulins G, A and M; complement components (C3, C4 and factor B), and blood lymphocyte subsets (CD3, CD4 and CD8). RESULTS: Total cholesterol serum concentrations showed a significant reduction after 6 months of dietary therapy (p = 0.008). After 6 months on a low-fat diet, lymphocyte T subset counts (CD3, CD4 and CD8) showed significant decreases (p < 0.01 to p < 0.003), but lymphocyte counts were always within normal ranges. There was also a significant correlation between changes in some lymphocyte T subset counts (CD3 and CD8) and changes in triglyceride serum concentrations (p < 0.05). CONCLUSIONS: A low-fat, low-cholesterol diet diminished CD3, CD4 and CD8 lymphocyte subset counts that are elevated in children with hypercholesterolemia. Dietary therapy, with emphasis on the intake of n-3 fatty acids, could be useful in the modulation of the immune response at the atheromatous plaque level.

Adolescent↗
PubMed2006

Severe sepsis exacerbates cell-mediated immunity in the lung due to an altered dendritic cell cytokine profile.

Severe sepsis leads to long-term alterations in the immune response of surviving individuals. We have modeled this alteration in host immunity by studying the survivors of severe experimental sepsis (murine cecal ligation and puncture), which were subsequently challenged with lung granuloma-inducing Schistosoma mansoni eggs. This granulomatous response is a well-studied cell-mediated immune reaction characterized by elevated levels of type-2 cytokines. Pulmonary granulomas induced by S. mansoni eggs in cecal ligation and puncture survivors were significantly larger and contained more eosinophils than granulomas in sham-operated mice. Significantly lower interleukin (IL)-12p40 mRNA and IL-12p70 protein levels were observed in the lungs of postseptic mice with developing granulomas, compared with controls. Postseptic mice had significantly fewer dendritic cells in the lungs during the granulomatous response. Isolated lung dendritic cells from postseptic mice at days 8 and 16 after S. mansoni egg challenge exhibited defective IL-12 synthesis but enhanced IL-10 synthesis after Toll-like receptor agonist challenge. Pulmonary transfection with an IL-12-expressing adenovirus in postseptic mice reversed the skewing of the pulmonary cytokine profile and normalized the lung granulomatous response. Our data indicate that severe sepsis shifts the pulmonary cytokine environment, presumably via effects on pulmonary dendritic cells, which in turn alters the lung cell-mediated immune response.

Animals↗
PubMed2002

[Persistence of immunity after hepatitis B vaccination].

The paper recalls different preparations of vaccines (including these containing S, preS1 and preS2 antigens), schemes of vaccinations and their effects. The possible causes of hyporeactivity to hepatitis B vaccines, both technical and dependent on deficiency of immunity, or immunogenetic profile of a vaccine were discussed. The persistence of anti-HBs responses after natural infection and post-vaccination was compared. Finally, a possibility of persistence of post-vaccination cellular immunity for at least 15 years was discussed.

Hepatitis B↗
PubMed2005

Immune system and hepatitis B virus infection.

The immune system plays an important role in determining the outcome of hepatitis B virus (HBV) infection. This is because recovery from of acute HBV infection is associated with a clear division in the profile of adaptive immune response. Multispecific antiviral CD4 and CD8 responses with a type 1 cytokine production can be observed in patients who recover from acute HBV infection. On the other hand, those who develop chronic infection tend to have a weak virus specific T cell response. Therapeutic strategies aimed at correcting this defective T cell reactivity could represent a complementary approach to the cure of chronic HBV infection.

Genetic Variation↗
PubMed1991

In vivo effects of neonatal administration of antiidiotype antibodies on experimental autoimmune myasthenia gravis.

The in vivo effects of neonatal administration of varying doses of anti-idiotype antibodies on serum anti-acetylcholine receptor (AChR) antibody titers, idiotype expression, and disease severity was studied in experimental autoimmune myasthenia gravis. Polyclonal affinity purified anti-idiotype antibodies and monoclonal anti-idiotype antibodies directed at anti-AChR monoclonal antibody 65 were administered in dosages varying from the nanogram to the microgram range. Mab 65 is directed against the main immunogenic region of mammalian AChR. In 1 out of 4 experiments administration of a nanogram dosage of anti-idiotype antibodies led to an enhanced anti-AChR antibody response after immunization with AChR. But no enhancing effect on idiotype expression could be demonstrated during this experiment. Adoptive transfer of spleen cells from rats pretreated with a nanogram dosage of anti-idiotype antibodies resulted in an significantly increased antibody response against rat AChR after immunization. From these experiments we conclude that in vivo administration of polyclonal or monoclonal anti-idiotypes does not reproduceably modify the serum antibody level against the acetylcholine receptor, nor influences the idiotype profile of the immune response. Secondly, the idiotype mediated manipulation of the immune response against large antigens, like the acetylcholine receptor, is clearly more complicated than that against small haptens. Adoptive transfer models, might be helpful in analysing the possibilities of anti-idiotype treatment in myasthenia gravis in more detail.

Animals↗
PubMed2002

Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses.

New cationic nanoparticles (SMBV) were evaluated for use as a nasal vaccine delivery system for two recombinant proteins: HBsAg and beta-galactosidase. Each protein was formulated with SMBV and intranasally administrated to non-anesthetized mice. In each model, the formulated protein induced high levels of specific serum IgG antibodies and cytotoxic T lymphocyte (CTL) responses. Moreover, specific IgA antibodies were found in nasal as well as in vaginal washes of intranasally immunized mice with the protein associated with SMBV. In contrast, no IgG or IgA antibodies and no CTL were detected in mice immunized with free protein. The detection of a CTL response and an increase in both IgG1 and IgG2a antibodies in serum suggest that SMBV amplifies both Th1 and Th2 responses without modifying the Th1/Th2 profile of the immune response induced by the natural protein. These data demonstrate the high potential of SMBV for use as a nasal delivery system for sub-unit vaccines.

Adjuvants, Immunologic↗
PubMed1999

Immune responses in asymptomatic HIV-1-infected patients after HIV-DNA immunization followed by highly active antiretroviral treatment.

Intensive chemotherapy is capable of reducing the viral load in HIV-1-infected individuals while infected cells are still present. A special property of DNA immunization is to induce both new CTL and Ab responses. We evaluated the possibility of inducing new immune responses in already infected individuals by means of DNA constructs encoding the nef, rev, or tat regulatory HIV-1 genes. Significant changes in viral loads and CD4+ counts were observed in four patients who started highly active antiretroviral treatment (HAART) during the immunization study. The DNA immunization induced Ag-specific T cell proliferation, which persisted up to 9 mo after the last DNA injection, and cytolytic activities but did not, by itself, reduce viral load. Increased levels of CTL precursor cells were induced in all nine DNA-immunized patients. The profile of IFN-gamma secretion observed when human PBMC were transfected with the nef, rev, and tat DNA resembled that found in the CTL activity (nef > tat > rev). Ab responses that occurred after immunizations were of a low magnitude. In accordance with the high IL-6 production induced by the nef DNA plasmid, IgG titers were highest in patients immunized with nef DNA. The initiation of HAART appears to contribute to the induction of new HIV-specific CTL responses, but by itself did not cause obvious re-induction of these activities.

AIDS Vaccines↗
PubMed2026

Systemic immune activation in hereditary cancer predisposition syndromes: a cross-sectional study.

BACKGROUND: Immune surveillance mechanisms contribute to the elimination of precancerous lesions in hereditary cancer predisposition syndromes (HCPSs). METHODS: By combining single-cell transcriptomics, multiparametric mass cytometry and cytokine profiling of the systemic immune environment in 391 individuals among whom 227 are living with HCPSs we investigated phenotypic alterations in cancer-free individuals with HCPS. RESULTS: A decrease in peripheral B cell abundance and their more differentiated phenotype have been confirmed both in breast cancer patients with germline pathogenic variants in BRCA1 (gpath(BRCA1)) and in patients living with Lynch syndrome (LS). Pre-cancer women with gpath(BRCA1) exhibited an activated phenotype of multiple immune cell lineages, similar to those with manifest disease. In LS, B cell phenotypes exhibited the largest changes in response to cancer eradication, while increased peripheral IL-6 levels was detected even in presymptomatic individuals with LS. CONCLUSIONS: HCPS-specific differences in the phenotype of the systemic immune system might be leveraged in future risk-reducing strategies.

Humans↗
PubMedDate not supplied

[Types of immune response in acute infectious diseases].

The author's concept on the system of self regulation of immune response is described. Four types of this response are proposed, which differ by total intensity of cytokine reaction, the development time as well as manifestation degree of non specific immunosuppression, and, most importantly, the profile of specific immune response to the antigens of the infective agent. These four types of immune response are closely linked with increased severity of clinical manifestations.

Acute Disease↗
PubMed2001

CpG DNA functions as an effective adjuvant for the induction of immune responses in aged mice.

The present studies demonstrate that the immunization of aged mice with Diphtheria toxoid in formulations containing unmethylated immunostimulatory CpG motifs, promotes the successful development of immune responses that are qualitatively and quantitatively comparable to those induced in young animals vaccinated in a similar manner. Aged mice given vaccines containing CpG oligodeoxynucleotides (ODNs) expressed primary and secondary systemic humoral immune responses having isotype profiles consistent with an enhancement in Th-1 type immunity. The ability to generate common mucosal immunity was also restored in aged animals given CpG ODN-containing vaccines. Dendritic cells (DCs) were determined to represent one of the cellular targets of CpG ODN activities in aged mice since restoration of immune function was observed when DCs from aged donors were pulsed with antigen and CpG ODNs, prior to injection into syngeneic young adult or aged recipients. Interestingly, antigen-pulsed DCs from young donors were fully capable of stimulating immune responses following their injection into syngeneic young adult or aged hosts, without a need for exposure to CpG ODNs. Although the mechanism(s) by which CpG DNA exerts its beneficial adjuvant effects on the aged immune system remains unclear, our findings suggest that the incorporation of CpG ODNs into vaccine formulations provided to the aged could prove useful in the development of more effective vaccines for the elderly.

Adjuvants, Immunologic↗
PubMed2001

Acid stress upregulated outer membrane proteins in clinical isolates of Neisseria gonorrhoeae, but not most commensal Neisseria.

Human immune serum recognition of outer membrane components from commensal and pathogenic Neisseria cultured under neutral and acidic conditions was investigated. Acid stress caused no detectable alterations in lipooligosaccharide migration and (or) staining, in outer membrane protein profiles, or in immune serum recognition of outer membrane components from Neisseria mucosa or Neisseria sicca. There was also no difference in the lipoologosaccharide electrophoretic pattern of acid- and neutral-grown Neisseria lactamica, but there were differences in outer membrane protein expression. The outer membrane protein alterations induced by acid stress in N. lactamica were not the same as those seen in isolates from patients with uncomplicated gonococcal infection, pelvic inflammatory disease, and disseminated gonococcal infection. Many differences were detected in the immune serum recognition of outer membrane components from acid- and neutral-cultured N. lactamica and from the clinical isolates of Neisseria gonorrhoeae, and these should be considered in vaccine design.

Bacterial Outer Membrane Proteins↗
PubMed1998

Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile.

The expression of Th2-skewed immunity against soluble protein Ags present in the normal environment is recognized as the primary cause of allergic inflammation in atopics. In contrast, nonallergic normal individuals display low level Th1-skewed immunity against the same Ags ("allergens"), which is perceived as conferring protection against Th2-dependent allergic sensitization. The type of T cell memory that develops against these Ags is currently believed to be the result of complex interactions between environmental and genetic susceptibility factors, which occur postnatally when the naive immune system directly confronts the outside environment. The results of the present study challenge this general concept. We demonstrate here for the first time that Th2-skewed responses to common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are present in virtually all newborn infants and are dominated by high level production of IL-10. Moreover, these responses are demonstrable within 24 h of culture initiation, arguing against a significant contribution from covert in vitro T cell priming and/or differentiation. These findings imply that the key etiologic factor in atopic disease may not be the initial acquisition of allergen-specific Th2-skewed immunity per se, but instead may be the efficiency of immune deviation mechanisms, which in normal (nonatopic) individuals redirect these fetal immune responses toward the Th1 cytokine phenotype.

Allergens↗