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At least 955 records · Page 53Linked to original sources
PubMed2006

A single immunization with a minute dose of a lentiviral vector-based vaccine is highly effective at eliciting protective humoral immunity against West Nile virus.

BACKGROUND: Lentiviral vectors, due to their capacity to transduce non-dividing cells, have become precious and worldwide used gene transfer systems. Their ability to efficiently and stably transduce dendritic cells (DCs) has led to their successful use as vaccination vectors for eliciting strong, specific and protective cellular immune responses mostly in anti-tumoral but also in anti-viral applications. However, the ability of lentiviral vectors to elicit an antibody-based protective immunity has, to date, not been evaluated. In the present study, we evaluated the potential of a lentiviral vector-based vaccine to elicit humoral immunity against West Nile virus (WNV). WNV is a mosquito-borne flavivirus that emerged in North America and causes encephalitis in humans, birds and horses. Neutralizing anti-WNV antibodies have been shown to be crucial for protection against WNV encephalitis. METHODS: The ability of lentiviral vector TRIP/sE(WNV), expressing the secreted soluble form of the envelope E-glycoprotein (sE(WNV)) from the highly virulent IS-98-ST1 strain of WNV, to induce a specific humoral response and protection against WNV infection was assessed in a mouse model of WNV encephalitis. RESULTS: Remarkably, a single immunization with a minute dose of TRIP/sE(WNV) was efficient at eliciting a long-lasting, protective and sterilizing humoral immunity, only 1 week after priming. CONCLUSIONS: This study broadens the applicability of lentiviral vectors as efficient non-replicating vaccines against pathogens for which a neutralizing humoral response is one active arm of the protective immunity. The TRIP/sE(WNV) lentiviral vector appears to be a promising tool for veterinary vaccination against zoonotic WNV.

Animals↗
PubMed1999

Immunization of RANTES expression plasmid with a DNA vaccine enhances HIV-1-specific immunity.

Cytokines play important roles in regulating immune response. This study evaluated the adjuvant effect of an expression plasmid encoding RANTES (regulated on activation normal T-cell expressed and secreted) chemokine on the immunity induced by a DNA vaccine. This vaccine consists of expression plasmids encoding the env and rev genes of human immunodeficiency virus type 1 (HIV-1). DNA vaccination with RANTES plasmid induced significantly higher titers of serum HIV-1-specific IgG and IgG2a antibodies than DNA vaccination alone on both intramuscular and intranasal immunization. This combination also increased HIV-1-specific cytotoxic T lymphocyte activity and delayed-type hypersensitivity. Intranasal immunization induced a higher titer of fecal secretory IgA antibody than intramuscular immunization. These results demonstrate that coadministration of RANTES plasmid dominantly induced HIV-1-specific cell-mediated immunity.

Adjuvants, Immunologic↗
PubMed1997

Protective immune responses induced by the immunization of mice with a recombinant bacteriophage displaying an epitope of the human respiratory syncytial virus.

We investigated whether a recombinant bacteriophage displaying a disease-specific protective epitope could be experimentally used as a vaccine to confer protection of immunized animals against infection. We genetically engineered a recombinant phage, fd, displaying at its surface a chimeric pIII coat protein fused to the previously identified protective epitope 173-187 from the glycoprotein G of the human respiratory syncytial virus (RSV). A selected recombinant fd phage elicited a strong immune response in mice, inducing a high level of circulating RSV-specific antibodies. Mice immunized with the recombinant phage acquired a complete resistance to RSV infection as evidenced by the lack of detectable virus particles in their lungs following intranasal challenge with live RSV. In contrast, a high level of virus particles was found in the lungs of either animals immunized with the wild-type fd phage or nonimmunized mice. To our knowledge, this is the first study to report the ability of a phage presenting an immunogenic peptide to prevent infection of immunized animals by a pathogen. This finding should facilitate the identification of pathogen-specific protective epitopes selected from random phage peptide libraries, as it is simpler and less expensive than the conventional method of synthesis and coupling of phage-specific peptide ligand sequences for immunization.

Amino Acid Sequence↗
PubMed1993

Two different mechanisms of immune-complex trapping in the mouse spleen during immune responses.

The capacity of immune-complex (IC) trapping was examined using purified horse radish peroxidase (HRP)-anti-HRP (PAP) on frozen sections of mouse spleen in vitro. We investigated the trapping mechanisms by applying the IC with or without fresh mouse serum added on the spleen sections of naive as well as immunized mice. When the PAP was applied alone, it mainly located on the macrophages in red pulp. In the splenic white pulp of immunized mice, PAP was trapped on follicular dendritic cells (FDC) in a small area of the germinal center whereas it scarcely bound to the splenic white pulp of non-immunized mice. An antibody against mouse Fc receptor (2.4G2) blocked the trapping but antibodies against mouse complement receptor (8C12, Mac-1 and 7G6) did not. When the PAP was applied mixed with fresh mouse serum, it bound on FDC in the primary follicles in the spleen of non-immunized mice. The density and area of IC trapping increased in the spleen of immunized mice. IC trapping in the presence of fresh mouse serum was blocked by the antibodies 8C12 and 7G6 but not by 2.4G2 or Mac-1.

Animals↗
PubMed1978

[Age and immunity: III. Circulating immune complexes in different age groups (author's transl)].

Circulating immune complexes were determined utilizing an immunofluorescence technique in sera of 271 healthy donors in different age groups. Practically no immune complexes were detected up to the age of 60. Among the donors ranging in age between 60 and 70 years, 20% revealed immune complexes in their sera. The incidence of circulating immune complexes increased up to 33% among the individuals between 70 and 75 years of age and up to 40% among those over 76 years. In view of earlier findings of decreased numerical and functional capacities of peripheral blood lymphocytes and functional capacities of peripheral blood lymphocytes and increased incidence of auto-antibodies, the observation, that the incidence of circulating immune complexes increases with age seems to support the hypothesis of an age-dependent immunological impairment. To what extent such an immunological insufficiency plays a role in the general aging process remains unknown. It can, however, explain some of the auto-immune diseases seen frequently among the elderly population.

Adult↗
PubMedDate not supplied

Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C: tetramer assay and therapeutic implications.

Both chronic hepatitis B and C virus (HBV and HCV) infections respond ineffectively to current antiviral therapies. Recent studies have suggested that treatment outcomes may depend on the development of type 1 T helper (Th1) and Th2 cell responses. Specifically, activation of Th1 immunity may play a major role in successfully treating hepatitis B and C. This model was revisited herein by evaluating immune responses in 36 HBV and 40 HCV patients with or without treatment, in an attempt to find a common immune mechanism for successful treatment. The immune responses in all examined cases were studied by peripheral blood mononuclear cell (PBMC) proliferation and cytokine responses to viral antigens, cytotoxic T lymphocyte (CTL) responses, enzyme-linked immunospot (ELISPOT) assay, and tetramer staining of virus-specific CD8+ T cells. The overall results revealed that all responders among both HBV- and HCV-infected cases displayed significantly higher PBMC proliferation to viral antigens with a predominant Th1 cytokine profile. Furthermore, the Th1-dominant responses were associated with significant enhancement of CTL activities and were correlated with ELISPOT data, while non-responders responded more weakly. During therapy, the numbers of tetramer-staining, virus-specific CD8+ T cells showed greater increases in responders than in non-responders (p = 0.001). The frequencies determined by the tetramer assay were approximately 200-fold higher than data estimated by limiting-dilution analysis. In conclusion, activation of Th1 immunity accompanied by enhancement of CTL activity during therapy is a common immune mechanism for successfully treating hepatitis B and C, and therefore may have important therapeutic implications.

Adult↗
PubMed1997

Nasal lymphoid tissue, intranasal immunization, and compartmentalization of the common mucosal immune system.

Mucosal application of vaccines with an appropriate adjuvant can induce immune responses at both systemic and mucosal sites, and therefore may prevent not only infectious disease, but also colonization of mucosal surfaces. Intranasal is more effective than intragastric immunization at generating earlier and stronger mucosal immune response. Nasal lymphoid tissue (NALT) and its local draining lymph nodes may retain long-term immune memory. IgA isotype switching, and the differentiation and maturation of IgA antibody-secreting cells (ASC) may occur before these cells migrate out of NALT, whereas IgG ASC responses require passage of the cells through draining lymph nodes of the NALT. Knowledge of whether immune memory cells can recirculate to and reside in the inductive sites other than their origin after encountering antigen will be helpful for understanding the compartmentalization of the common mucosal immune system as well as for determining the best route for delivering a mucosal vaccine against a particular pathogen.

Administration, Intranasal↗
PubMed2000

Kinetics of cells and cytokines during immune-mediated inflammation in the mammary gland of cows systemically immunized with Staphylococcus aureus alpha-toxin.

OBJECTIVE: To examine changes in inflammatory mediators, lymphocyte subpopulations and neutrophil activation that occur during an immune-mediated recruitment of neutrophils in the mammary gland. SUBJECTS: 11 clinically healthy cows. TREATMENT: 5 cows received 2 subcutaneous injections of 30 microg of alpha-toxin of Staphylococcus aureus, two months apart. Three months after the last immunization, 5 microg of alpha-toxin were injected, via the teat end, in one randomly selected quarter of the 5 immunized cows and of the 6 unimmunized cows (control group). METHODS: Blood and milk samples were collected at several times during 4 days post-challenge. Blood and milk cells were purified to be stained with specific mAbs and analysed by flow cytometry, or to be used for cytokine RT-PCR. Bovine serum albumin, haptoglobin, cytokines and C5a were also analysed in milk or plasma samples using radial immunodiffusion assay or ELISA. RESULTS: Large amounts of cells (> 1 million/ml of milk) were recruited in the quarters of the immunized cows, whereas no recruitment occurred in the control group. In blood of immunized animals, haptoglobin was present and expression of surface adhesion molecules on neutrophils was modified whereas no change was observed concerning the lymphocyte subpopulations. On milk-derived neutrophils, the expression of CD11b and CD18 was upregulated compared to blood, in contrast to CD62L that was downregulated. The CD8+ cells were recruited as soon as 12 h post-challenge, in contrast to the CD4+ cells, 96 h post-challenge. No IL-1beta, TNF-alpha, IL-8 and C5a were detected using ELISA. mRNA of IL-1alpha, IL-1beta, IL-6, TNF-alpha, IL-8 and IL-12 were found in almost all the samples. CONCLUSIONS: The immunization triggered an early and massive neutrophil recruitment from the blood into the milk compartment as well as the recruitment of a cytotoxic/suppressor lyphocyte population during the early acute phase response. These results could help to devise new vaccinal strategies to fight against staphylococcal mastitis.

Animals↗
PubMed2006

The distinct effects of three tandem repeats of C3d in the immune responses against tumor-associated antigen hCGbeta by DNA immunization.

Several examples have shown that C3d3, when fused to a corresponding antigen, had a strong adjuvant effect on certain specific antibody production. In a previous study, we attempted to prove that this was the case of the human chorionic gonadotrophin beta chain (hCGbeta)-induced immunity following DNA vaccination. However, we found that C3d3 when fused to hCGbeta inhibited rather than enhanced the antigen-specific immune response. In the present study, using hCGbeta DNA vaccine preparations, we demonstrated that C3d3 inhibited the antigen-specific humoral antibody response and several other immune responses, such as the hCGbeta specific lymphoproliferation. Such inhibitory effects of C3d3 were not related to the expression level of the target protein, the gender of the test mice, or the vector used. Contrastingly, C3d3 fused with the envelope protein of hepatitis B virus (PreS2/S) used as a control system resulted in the enhancement of both humoral and cell-mediated antigen-specific immune responses against HBV-preS2/S, which was consistent with other groups' adjuvant-effect findings. We further showed that the mechanisms involved in the inhibitory effect of C3d3 might be possible due to impairing the function of antigen presenting B lymphocytes and reducing the expression of transcription factors (T-bet and GATA-3) and cytokine IL-4. Collectively, unlike its usual expected adjuvant function, the fusion of C3d3 with the tumor-associated antigen hCGbeta was found to inhibit both humoral and cell-mediated antigen-specific immune responses. These findings indicate that research concerning tumor immune escapes and vaccine designs require further extensive attention.

Adjuvants, Immunologic↗
PubMed2000

Experimental immune-mediated blepharoconjunctivitis in rats induced by immunization with ragweed pollen.

BACKGROUND: A study was performed to compare the effects of immunization with ragweed pollen (RW) in two different adjuvants on the characteristics of a previously described model of experimental immune-mediated blepharoconjunctivitis (EC) in rats. METHODS: Lewis or Brown Norway (BN) rats were immunized with 100 microg of RW in emulsion with aluminum hydroxide [Al(OH)3] or complete Freund's adjuvant (CFA). Three weeks later, the animals were challenged with eye drops containing RW in PBS. Twenty-four hours after topical challenge, eyes, blood, and lymph nodes were obtained for histology, measurement of antigen-specific antibodies, and proliferation or cytokine assays, respectively. In addition to active immunization, recipients of RW-primed lymph node cells were challenged and evaluated as above. RESULTS: RW in both adjuvants induced infiltration with predominantly mononuclear cells in Lewis rats and eosinophils in BN rats. As well as active immunization, eosinophils were detected only in BN rats by adoptive transfer of cells. Lymphocyte proliferative responses to RW were high in immunized Lewis rats when CFA was used as an adjuvant. In contrast, proliferative responses in BN rats were higher when Al(OH)3 was used. RW-specific IgE was detected only in BN rats. There were no significant differences in RW-specific IgG1/IgG2a ratio among the four groups. Lewis rats had higher level of RW-specific interferon-gamma in the culture supernatant. CONCLUSIONS: The characteristics of EC are different in Lewis and BN rats, dependent on the genetic background of the rat strains. The response to RW was similar to other previously used antigens, such as ovalbumin.

Allergens↗
PubMed2005

Humoral and cellular immune responses in BALB/c and C57BL/6 mice immunized with cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens, in acute experimental Trypanosoma cruzi infection.

In previous studies, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) proteins induced specific humoral and cellular immune responses in susceptible and resistant mice in the absence of Trypanosoma cruzi infection with a significant induction of the Interferon-gamma (IFN-gamma) production in those animals. In this follow-up paper, the immunostimulatory and protective effects of these proteins were evaluated by immunizing with CRA or FRA antigens, BALB/c and C57BL/6 mice and challenging with a T. cruzi (Y strain). Both proteins induced humoral response with high levels of IgG isotypes as well as cellular immunity with high levels of IFN-gamma when compared to controls. However, the lymphocyte proliferative response was minimal. The survival rate at 30 days post-infection was significant in CRA (60%) or FRA (50%)--immunized BALB/c mice and CRA (83.3%)--immunized C57BL/6 mice. Taken as a whole these findings indicate that CRA and FRA are immunogenic and potentially important for protective immunity.

Animals↗
PubMed1992

Behavior of the idiotypic network in conventional immune responses. I. Kinetics of idiotypic and anti-idiotypic antibodies following immunization with T-independent and T-dependent antigens.

A minimal requirement in investigations of the behavior of the idiotypic network during immunization is the ability to quantitate both the idiotypic (Ab1) and anti-idiotypic (Ab2) responses. Quantitation of Ab2 in serum is complicated by the simultaneous presence of Ab1, so that Ab1-Ab2 immune complexes escape detection. In contrast, immune complexes should not complicate the enumeration of Ab2-producing lymphocytes in a hemolytic plaque assay. This study utilizes a procedure that allows detection of Ab2-producing cells in such an assay. The procedure relies upon the insertion of the appropriate antibody (Ab1) into the membrane of indicator SRBC through a covalently attached dipalmitoyl phosphatidylethanolamine (DPPE) tail. When the Ab2 response following murine immunization with DNP-Ficoll was analyzed using such an assay, peak plaque-forming cell (PFC) numbers were found to coincide with peak Ab1 PFC numbers in both the primary and secondary response. In addition, this Ab2 response was found to be T independent. The murine immune response to DNP-HGG demonstrated a peak Ab2 PFC response which followed the peak Ab1 PFC response after both primary and secondary immunization. This Ab2 response appeared to be T dependent. The secondary responses to both DNP-Ficoll and DNP-HGG showed increased levels of Ab2 PFC and decreased levels of Ab1 PFC in comparison to the primary responses to the same antigens, suggesting that immunoregulation may occur within these idiotypic networks.

Animals↗
PubMed1978

The effect of clofibrate and pyridinol carbamate on the circulating immune complexes and cellular immune response in experimental atherosclerosis.

Cholesterol-fed rabbits were treated with clofibrate, pyridinol carbamate and with both drugs simultaneously. The quantity of circulating immune complexes in the sera of the animals was measured weekly and the migration inhibition test was carried out in the 12th week of the experiment. The trend of the changes in the concentration of the immune complexes was rather similar to that of the cellular immune response. Compared with the values obtained in the control animals, in the cholesterol-fed group a markedly higher level of immune complexes and a significant migration inhibition could be detected. The administration of clofibrate or pyridinol carbamate alone had no effect on the concentration of immune complexes. Pyridinol carbamate did not influence the migration inhibition; however, it became similar to the healthy controls in the clofibrate-treated group. Simultaneous treatment with both drugs resulted in a decrease in the quantity of immune complexes and a diminution of the migration inhibition.

Animals↗
PubMed1989

Stress and immunity: an integrated view of relationships between the brain and the immune system.

The old notion that stress exacerbates the progression of physical illness via its corticosteroid-mediated immunosuppressive effects must be revised. Experimental and clinical studies demonstrate that both laboratory and natural stressors alter the activities of lymphocytes and macrophages in a complex way that depends on the type of immune response, the physical and psychological characteristics of the stressor and the timing of stress relative to the induction and expression of the immune event. The influences of stress on immunity are mediated not only by glucocorticoids but also by catecholamines, endogenous opioids and pituitary hormones such as growth hormone. Sensitivity of the immune system to stress is not simply fortuitous but is an indirect consequence of the regulatory reciprocal influences that exist between the immune system and the central nervous system. The immune system receives signals from the brain and the neuroendocrine system via the autonomic nervous system and hormones and sends information to the brain via cytokines. These connections appear to be part of a long-loop regulatory feedback system that plays an important role in the coordination of behavioral and physiological responses to infection and inflammation.

Animals↗
PubMed1984

The influence of Aclacinomycin A on the immune response and on experimental immune disorders.

The anti-cancer drug Aclacinomycin A (ACM) was able to inhibit the humoral immune response of mice against sheep red blood cells. This could be demonstrated in the formation of antibody secreting cells (PFC) and serum antibody titers, when ACM was administered either together with the antigen or three days after antigen application. Cellular immunity was not affected by the drug. In two murine Graft-vs-Host (GvH) disease models leading to two different B cell dependent auto-immune diseases (immune complex glomerulonephritis and immune hemolytic anemia) a protective effect of ACM was observed when it was administered at the time of the graft. The application of ACM in the induction phase mitigated the development of glomerulonephritis and prevented animals from dying due to hemolytic anemia. Only a slight therapeutical effect was observed when ACM was given after the appearance of clinical symptoms. In a T cell induced auto-immune disease (experimental allergic encephalomyelitis (EAE], ACM had no discernible effect on the course of the disease. It seems that the therapeutic effects of ACM on GvH-diseases are mediated via suppression of B-lymphocytes.

Aclarubicin↗
PubMed1982

Immune response to polyoma tumor cells in mice--III. Stimulation of tumor cell growth in vitro by spleen cells from immunized animals.

We have evaluated the stimulation of target cell growth in vitro by spleen cells from mice which were immunized with polyoma-transformed cells and other tumor and non-tumor antigens. Stimulation was particularly seen under conditions of immunization that were suboptimal for the production of specific cytotoxicity. Significant stimulation of polyoma target cell growth was observed by lymphocytes from mice immunized against 10(5) Py 4198 tumor cells. This stimulation of target cell growth was not confined to polyoma-transformed cells only. Cells transformed by SV40, H-MuSV and non-transformed cells like 3T3 and embryo fibroblasts were also stimulated. Immunization of mice with syngeneic embryo fibroblasts also resulted in stimulation of tumor cell growth by the spleen cells from the immunized mice. However, the growth stimulation was less consistent and did not occur in all target cells tested. The specificity of immunostimulation was further studied with the Moloney sarcoma virus (M-MuSV) system; an antigenically distinct tumor system. Spleen cells from M-MuSV tumor-bearing mice stimulated cell growth in vitro not only against MuSV-transformed cells but also with SV40-transformed and polyoma-transformed cells as targets. Significant stimulation of target cell growth was also observed by spleen cells from mice that were immunized against 'non-pertinent' antigens, e.g. sheep red blood cells and allogeneic (C57B 1/6) spleen cells.

Animals↗
PubMed2004

Immune response after adjuvant mucosal immunization of mice with inactivated influenza virus.

Satisfactory mucosal immunity in the respiratory tract is very important for protection against influenza. It can be achieved only by mucosal immunization. Mucosal vaccination with inactivated influenza virus may not be sufficiently effective and suitable adjuvants are therefore sought. We tested intratracheal immunization of mice with inactivate B type influenza virus in a mixture with formolized G+ bacterium Bacillus firmus, whose adjuvant effects have previously been documented in another system. The treatment resulted in a marked increase of both systemic and mucosal antibody response in IgG and IgA classes. Stimulation of T lymphocytes after adjuvant immunization was very mild, no proliferation taking place after specific stimulation with antigen in vitro. However, slightly increased systemic (spleen) and local (lungs) production of cytokines without perceptible Th1/Th2 polarization was determined. B. firmus is an efficient adjuvant in respiratory tract immunization while with subcutaneous immunization it lowers the antibody response.

Adjuvants, Immunologic↗
PubMed2006

Skin-derived dendritic cells induce potent CD8(+) T cell immunity in recombinant lentivector-mediated genetic immunization.

The skin contains readily accessible dendritic cells (DCs) with potent antigen presentation function and functional plasticity enabling the integration of antigen specificity with environmentally responsive immune control. Recent studies challenge the established paradigm of cutaneous immune function by suggesting that lymph node-resident DCs, rather than skin-derived DCs (sDCs), are responsible for eliciting T cell immunity against cutaneous pathogens including viral vectors. We show that cutaneous delivery of lentivirus results in direct transfection of sDCs and potent and prolonged antigen presentation. Further, sDCs are the predominant antigen-presenting cells for the induction of potent and durable CD8(+) T cell immunity. These results support the classical paradigm of cutaneous immune function and suggest that antigen presentation by sDCs contributes to the high potency of lentivector-mediated genetic immunization.

Animals↗