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PubMed1998

Persistence of hepatitis B vaccine immune protection and response to hepatitis B booster immunization.

AIM:To identify the persistence of immune protection of China-made, plasma derived hepatitis B vaccine after infancy immunization and the time table of booster immunization.METHODS:A cross-sectional follow-up study and an experimental study on booster were used for the evaluation of the serological effect 7 years after vaccination and the antibody anamnestic response. Radioimmunoassay was used for the detection of hepatitis B virus markers. RESULTS:The protective anti-HBs positive rates of 1018 children, who were vaccinated according to the regimen of three doses of 10 &mgr;g hepatitis B vaccine in their infancy, declined from 75.0% during the first two years to 48.2% in the 7th year after the first dosage, however, the positive rates for HBsAg and anti-HBc always fluctuated at a low frequency. A total of 144 subjects aged 6 or 7 years, who were negative for both HBsAg and anti-HBc before booster, were selected from 1018 children of the follow-up study, and boosted with 1&mgr;g intradermally or 2&mgr;g hypodermically hepatitis B vaccines. Their anti-HBs GMT and anti-HBs positive rates were 190.6mIU/ml and 89.6% in the first month after booster,significantly higher than 14.7mIU/ml and 54.9% before booster (P < 0.01), and declined back to 25.3mIU/ml and 75.5% in the 12th month; among 65 children with the anti-HBs negative before booster, 40 had a level of anti-HBS< = 100mIU/ml one month after booster, suggesting retention of immune memory in most of them.CONCLUSION:No need for revaccination against hepatitis B in the 7th year after the initial immunization due to better persistence of immune protection of the vaccine and retention of immune memory to hepatitis B virus in the vast majority of the vaccinees.

Journal Article↗
PubMed2002

Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats.

AIM: To determine whether Salmonella Typhimurium (STM)in gastrointestinal tract can induce the functional activation of brain, whether the vagus nerve involves in signaling immune information from gastrointestinal tract to brain and how it influences the immune function under natural infection condition. METHODS: Animal model of gastrointestinal tract infection in the rat was established by an intubation of Salmonella Typhimurium (STM) into stomach to mimic the condition of natural bacteria infection. Subdiagphragmatic vagotomy was performed in some of the animals 28 days before infection. The changes of Fos expression visualized with immunohistochemistry technique in hypothalamic paraventricular nucleus (PVN) and superaoptic nucleus (SON) were counted. Meanwhile, the percentage and the Mean Intensities of Fluorescent (MIFs) of CD4+ and CD8+ T cells in peripheral blood were measured by using flow cytometry (FCM), and the pathological changes in ileum and mesenteric lymph node were observed in HE stained sections. RESULTS: In bacteria-stimulated groups, inflammatory pathological changes were seen in ileum and mesenteric lymph node. The percentages of CD4+ T cells in peripheral blood were decreased from 42%+/-4.5% to 34%+/-4.9% (P<0.05) and MIFs of CD8+ T cells were also decreased from 2.9+/-0.39 to 2.1+/-0.36 (P<0.05) with STM stimulation. All of them proved that our STM-infection model was reliable. Fos immunoreactive (Fos-ir) cells in PVN and SON increased significantly with STM stimulation, from 189+/-41 to 467+/-62 (P<0.05) and from 64+/-21 to 282+/-47 (P<0.05) individually, which suggested that STM in gastrointestinal tract induced the functional activation of brain. Subdiagphragmatic vagotomy attenuated Fos expression in PVN and SON induced by STM, from 467+/-62 to 226+/-45 (P<0.05) and from 282+/-47 to 71+/-19 (P<0.05) individually, and restored the decreased percentages of CD4+ T cells induced by STM from 34%+/-4.9% to original level 44%+/-6.0% (P<0.05). In addition, subdiagphragmatic vagotomy itself also decreased the percentages of CD8+ T cells (from 28%+/-3.0% to 21%+/-5.9%, P<0.05) and MIFs of CD4+ (from 6.6+/-0.6 to 4.9+/-1.0, P<0.05) and CD8+ T cells (from 2.9+/-0.39 to 1.4+/-0.34, P<0.05). Both of them manifested the important role of vagus nerve in transmitting immune information from gut to brain and maintaining the immune balance of the organism. CONCLUSION: Vagus nerve does involve in transmitting abdominal immune information into the brain in STM infection condition and play an important role in maintenance of the immune balance of the organism.

Animals↗
PubMed2000

Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization.

CTL together with anti-envelope Abs represent major effectors for viral clearance during hepatitis B virus (HBV) infection. The induction of strong cytotoxic and Ab responses against the envelope proteins after DNA-based immunization has been proposed as a promising therapeutic approach to mediate viral clearance in chronically infected patients. Here, we studied the CTL responses against previously described hepatitis B surface Ag (HBsAg)-HLA-A*0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transgenic mice. The animal model used was Human Human D(b) (HHD) mice, which are deficient for mouse MHC class I molecules (beta(2)-microglobulin(-/-) D(b-/-)) and transgenic for a chimeric HLA-A*0201/D(b) molecule covalently bound to the human beta(2)-microglobulin (HHD(+/+)). Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carrying HBsAg induced CTL responses against several epitopes in each animal. This study performed on a large number of animals described dominant epitopes with specific CTL induced in all animals and others with a weaker frequency of recognition. These results confirmed the relevance of the HHD transgenic mouse model in the assessment of vaccine constructs for human use. Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-gamma-secreting CD8(+) T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans. This suggests that responses induced by DNA immunization could have the same immune potential as those developing during natural HBV infection in human patients.

Alleles↗
PubMed2001

HIV mucosal vaccine: nasal immunization with rBCG-V3J1 induces a long term V3J1 peptide-specific neutralizing immunity in Th1- and Th2-deficient conditions.

In the vaccine strategy against HIV, bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is considered to be one of potential vectors for mucosal delivery of vaccine Ag. We analyzed the induction of the Ag-specific Ab response by nasal immunization with recombinant BCG vector-based vaccine (rBCG-V3J1) that can secrete the V3 principal neutralizing epitope of HIV. Mice were nasally immunized with rBCG-V3J1 (10 microg) three times at weekly intervals. Four weeks after the initial immunization, high titers of V3J1-specific IgG Abs were seen in serum. These high levels of HIV-specific serum IgG responses were maintained for >12 mo following nasal immunization without any booster immunization. V3J1-specific IgG-producing cells were detected in mononuclear cells isolated from spleen, nasal cavity, and salivary gland of the nasally vaccinated mice. Nasal rBCG-V3J1 also induced high levels of prolonged HIV-specific serum IgG responses in Th1 (IFN-gamma(-/-))- or Th2 (IL-4(-/-))-immunodeficient mice. Further, IgG3 was highest among V3 peptide-specific IgG subclass Ab responses in these immunodeficient mice as well as in wild-type mice. In addition, this Ag-specific serum IgG Abs induced by nasal immunization with rBCG-V3J1 possessed the ability to neutralize clinical isolate of HIV in vitro. These results suggested that the nasal rBCG-V3J1 system might be used as a therapeutic vaccine in addition to a prophylaxis vaccine for the control of AIDS.

AIDS Vaccines↗
PubMed1999

The immune system as anti-tumor sentinel: molecular requirements for an anti-tumor immune response.

The concept behind immune surveillance against cancer is that tumor cells continuously develop, but that there may not be clinical evidence of their presence because the immune system recognizes the cells as foreign and destroys them. A clear role for the immune system in preventing and/or eliminating tumors is emerging as insights into the molecular requirements for the induction and effector function of cytolytic T lymphocytes (CTL) have been gained. Using murine tumor rejection models, the role of particular molecular components of the immune system in controlling tumor growth has been defined. However, tumor rejection does not always occur spontaneously in vivo, indicating that defects in the generation or execution of an anti-tumor immune response may be common. Understanding defects when they arise should allow for development of new therapeutic approaches in tumor-bearing individuals. Many clinical studies are underway to test strategies to induce or heighten an antitumor immune response in cancer patients.

Animals↗
PubMed1999

[Specific immune responses in H-2d mice after DNA immunization of HBV core gene].

OBJECTIVE: To observe the specific immune responses in H-2d mice after DNA immunization of HBV core gene. METHODS: The DNA vaccine (pJW4303/HBc) was constructed by inserting HBV core gene fragment into the reading frame of plasmid pJW4303. Both methods of gene gun and intramuscular immunization were used in this experiment. Anti-HBc (IgG) and its isotypes (IgG1, IgG2a) in mice sera were detected by ELISA. HBcAg specific cytotoxic T lymphocyte (CTL) activity was measured by 51Cr release assay. RESULTS: The expression of HBcAg was confirmed by ELISA and Western-blot in 293T cells transfected with pJW4303/HBc. The end-point titers of serum anti-HBc in immunized mice were 1: 328,050 (gene gun method) and 1:109,350 (intramuscular method). In both groups of gene gun and intramuscular immunization IgG2a level was slightly higher than IgG1. HBcAg specific CTL activities were 51. 1% in gene gun group and 55.2% in intramuscular group. CONCLUSION: In this experiment the DNA vaccine of pJW4303/HBc shows strong antigenecity in both cellular and humoral immunity.

Animals↗
PubMed2000

[Determination of antibodies after immunization with the FSME-Immun vaccine].

During 1997-1999 607 sera were obtained from subjects immunized with vaccine FSME-Immun. The presence of antibodies was assessed using EIA TBEV-Ig TEST-Line tests, Clinical Diagnostics, Immunozym FSME of Immuno Co. and the virus neutralizing test. Between the results of tests sufficient correlation was not found to allow valid evaluation of the presence of postvaccination antibodies by several methods. When using the Immunozyme FSME test it was found that on the day of administration of the 4th dose of vaccine 15 subjects of 94 had an antibody titre equal to or < 126 VIEU/ml, on the day of administration of the 5th dose this was the case in 5 of 13 immunized subjects. After administration of the 3rd, 4th and 5th dose adequate, i.e. at least three-year immunity, was acquired, depending on age, by 64.1-97.9% of the immunized subjects. As antibody titres higher than 600 VIEU/ml in different age groups were recorded only in 20.0-61.7% of the subjects, the authors do not consider it desirable in subjects immunized with the Austrian vaccine to prolong the time interval between vaccinations beyond three years.

Adolescent↗
PubMed1997

[An animal model for the mucosal immunization with the surface protein antigen P1 from streptococcus mutans and immune enhancement of cholera toxin].

To study the immune enhancement of cholera toxin by developing an mucosal immune animal model, SD rats were immunized using different antigen composition through intragastric route (I.G). The results showed that the effects of immunization became stronger after P1 was conjugated to cholera toxin B subunit (CTB) or procholeragenoid (PCG). Even microgram dose of P1 could induce the rising of anti-P1 SIgA antibodies in the rat's saliva, but the antibodies risied little without this adjuvant. These implayed that the conjugation was much necessary in IG immunization. The immune enhancement of PCG was greater than that of CTB.

Animals↗
PubMed1976

Autologous immune complex nephropathy. I. Sequential study of immune complex deposition, ultrastructural changes, proteinuria, and alterations in glomerular sialoprotein.

Experimental evidence suggests that barriers to glomerular filtration of macromolecules exist at the glomerular basement membrane itself and at the level of the epithelial cell and epithelial slit pores. The distribution of negatively charged glomerular sialoprotein (GSP) at the latter site and the reduction in histochemical staining for GSP reported in several clinical and experimental glomerular diseases suggest a role for this material in the regulation of glomerular permeability. Alternatively, reductions in GSP associated with proteinuria may reflect only epithelial cell swelling consequent to the proteinuria. The sequence of subepithelial immune complex deposition, epithelial cell swelling and foot process fusion, alterations in histochemical staining for GSP, and development of proteinuria was studied in 12 Lewis rats biopsied weekly during development of autologous immune complex (Heymann) nephropathy. Deposition of IgG was detectable 3 weeks after antigen injection by immunofluorescence. Electron-dense deposits were first seen by electron microscopy coincident with the appearance of complement at week 4. Proteinuria began at 6 to 8 weeks, 3 to 5 weeks after detectable immune complex deposition. Proteinuric animals had marked subepithelial immune complex deposition and extensive epithelial cell swelling and foot process fusion. Despite these changes, there was no detectable reduction in staining for GSP until week 14, 6 to 8 weeks after onset of proteinuria. Reductions in GSP apparently do not play a role in altering glomerular permeability early in autologous immune complex (Heymann) nephropathy, and proteinuria and epithelial cell swelling can be present in this model without detectable changes in GSP. These findings suggest that early alterations in GSP reported in some other proteinuric disorders may be of pathogenetic significance rather than simply a reflection of changes in epithelial cell morphology secondary to proteinuria. In this experimental model of membranous nephropathy, immunofluorescence was more sensitive than electron microscopy in the early detection of immune deposits.

Animals↗
PubMed2004

[Adenovirus mediated expression of interleukin 12 regulating hepatitis C virus E2 gene immunization-induced immune response].

OBJECTIVE: To observe the regulating effect of hepatitis C virus (HCV) envelop (E) 2 gene immunization-induced immune responses by adenovirus mediated interleukin 12 (IL-12). METHODS: HCV E2 protein was expressed and purified from NIH 3T3 and then used as an antigen to detect antibodies against HCV E2. With 51Cr release, SP2/0 expressing HCV E2 was used as target cell to detect specific cytotoxic T lymphocytes (CTL) response; adenovirus recombined IL-12 was propagated by 293 cell. HCV E2 recombinant and adenovirus recombined IL-12 were injected into the quadriceps femoris muscles and abdominal cavities of 6-8 weeks old BALB/C mice. Sera were collected at 2, 3, and 4 weeks and detected for antibodies for E2. Spleen cells isolated at 4 weeks were analyzed for specific CTL response. RESULTS: It was found that expression of IL-12 at an undetectable level did enhance HCV E2 gene immunization-induced CTL activity and there was no effect on its hormonal immune response. CONCLUSION: Using adenovirus to express interleukin 12 was helpful for regulation of HCV E2 gene immunization-induced immune response. Combined HCV E2 and IL-12 can render a strong anti-HCV CTL activity and may be of use in the development of HCV gene vaccine in the future.

Adenoviridae↗
PubMed1992

Precipitated immune complexes of IgM as well as of IgG can bind to rabbit polymorphonuclear leucocytes but only the immune complexes of IgG are readily phagocytosed.

We have shown by in vitro experiments, using immunofluorescence techniques, that precipitated immune complexes of IgM antibodies and ovalbumin (ICIgM) are able to bind to rabbit blood polymorphonuclear leucocytes (PMN), as well as immune complexes of IgG antibodies (ICIgG). This binding capacity for both classes of immune complexes is exhibited by more than 80% of the PMN cell population and is independent of Ca2+ in the medium. For ICIgG the binding to PMN can be completely inhibited by preincubation of the cells with soluble IgG used at physiological concentrations (competition for the Fc gamma receptors) while for ICIgM there is no such inhibition by fluid-phase IgM. After binding to the leucocytes there was a striking difference in the fate of ICIgM and ICIgG: whereas the ICIgG was readily phagocytosed (endocytosed), the ICIgM remained mostly on the cell surface, being only poorly endocytosed after 1 hr incubation at 37 degrees. This was demonstrated by a quantitative fluorimetric method developed to assay phagocytosis of immune complexes, and was confirmed by a qualitative fluorescence quenching technique. These results may have implications for understanding the fate of these classes of immune complexes formed in circulation or deposited in tissues, and the participation of PMN in inflammatory reactions and tissue injury in immune complex diseases.

Animals↗
PubMed1978

Abnormalities in humoral and cellular immune activity in pancreatitis. I. Study of the humoral immune system.

The abnormalities of the humoral immune phenomena in pancreatitis may be summarized on the grounds of published evidence and of the present results as follows: 1. Circulating anti-pancreas antibodies are present in acute pancreatitis as also after its cure, and in chronic pancreatitis. 2. The appearance of soluble immune complexes in pathological amounts was demonstrated in the sera of the patients by radiobioassay in acute pancreatitis of identified aetiology 3 to 4 weeks after onset. On the evidence of follow-up studies over 1 to 8 months the immune complexes were found to persist at increased levels after complete cure of acute pancreatitis. Soluble immune complexes were demonstrable in pathological amounts in the cases of chronic pancreatitis as well. 3. In acute pancreatitis the total serum complement titres decline fast and after a few weeks persistent hypocomplementaemia develops in a number of cases. 4. The possible role of circulating soluble immune complexes and of the complement system in pancreatitis is discussed, and it is suggested on the grounds of the present data that acute pancreatitis is associated with a specific and nonspecific immune sensitization, still demonstrable in a number of cases after a few months.

Adult↗
PubMed1987

Endotoxin-induced auto-immunity in mice. I. Time and dose dependence of production and serum levels of antibodies against bromelain-treated mouse erythrocytes and circulating immune complexes.

Injection of mice with endotoxin results in the formation of auto-antibodies and the appearance of soluble immune complexes in the blood. In this study the relationship between the production and serum levels of autohaemolysins and circulating immune complex titres was investigated. Immune complexes were detected by a solid-phase C1q-binding assay and found to contain antibodies of the IgM, but not of the IgG class. Individual mice showed marked differences as to their splenic plaque-forming cells, serum autohaemolysin, and circulating immune complex responses, both in kinetic studies and dose-response experiments. The dissociation between production and serum levels of auto-antibodies was ascribed to extrasplenic synthesis or a disproportionate production per plasma cell. The independent behaviour of the circulating immune complex response could, at least partially, be attributed to differential complement-dependent clearance from the circulation. The implications of our findings for the laboratory diagnosis of auto-immunity at the blood level are being discussed.

Animals↗
PubMed1986

Circulating immune complexes associated with decreased complement-mediated inhibition of immune precipitation in sera from patients with bacterial endocarditis.

The sera of patients with bacterial endocarditis frequently contain high levels of circulating immune complexes. In in vitro assays these sera have been shown to be deficient in the complement mediated inhibition of immune precipitation (immune complex solubilization) although C3 and C4 levels were often normal. The deficiency is due to the presence of a factor which also inhibits the ability of normal serum to solubilize immune complexes. This inhibitor is possibly rheumatoid factor which is frequently detected in endocarditis. Serial studies on 16 patients showed the levels of immune complexes, the ability to prevent immune precipitation and rheumatoid factor to correlate with disease activity. The similarity of the findings to those in rheumatoid arthritis are discussed.

Adult↗
PubMed1985

Nicolas Andry Award, 1984. Deleterious interactions of immune complexes in cartilage of experimental immune arthritis. I. The erosion of pannus-free hyaline cartilage.

Immune complexes were detected by plain and immunoelectron microscopy amongst electron-dense material that rapidly formed and extended over and into the cartilaginous surfaces of immune arthritic rabbits' knees. The sinuous extension of electron-dense material into the surface matrix was associated with fragmentation and detachment, resulting in erosions. The findings implicate the formation of immune complexes in the destructive process of the matrix. Since the eroded pannus-free matrix of rheumatoid cartilage surfaces contains extensive concentrations of immune complexes, the data of this immune arthritis model suggest a causative relation between immune complexes and matrix loss in rheumatoid arthritis.

Animals↗
PubMed1977

Immunization of mice against Trypanosoma cruzi. The effect of size of dose, and route of injection, of immunizing and challenge inocula.

Groups of CD-1 mice were immunized with a vaccine prepared from freeze-thawed cultured epimastigotes of Trypanosoma cruzi, strain Y, with or without saponin as adjuvant. The vaccine was injected by the subcutaneous (s.c.) or intraperitoneal (i.p.) route. Immunized and control mice were challenged with homologous blood trypomastigotes by the s.c. or i.p. route and the former route was found to produce a far more severe and uniform infection in both control and immunized mice. Subcutaneous challenge of vaccinated mice demonstrated an improvement in the protective effect of the vaccine when saponin was included, but following i.p. challenge equally good protection was achieved with or without saponin. Thirty-nine of 40 immunized mice challenged i.p. survived the infection. A strong correlation was shown between the size of both immunizing and challenge inocula and the protective effect of the vaccine. Immunized mice which survived challenge were resistant to reinfection, but all were shown to carry persistent sub-patent parasitaemia.

Adjuvants, Immunologic↗
PubMed1982

Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). I. H-2 restriction of the murine humoral immune response to the a and d determinants of HBsAg.

In hepatitis B virus (HBV) infection correlation of disease activity with major histocompatibility complex (MHC) antigens has been suggested. However, no data are available regarding the nature and regulation of the immune response to the surface viral protein (HBsAg). This consideration and the current emphasis on production of an HBV vaccine led us to investigate the humoral immune response to HBsAg in inbred strains of mice to assess genetic factors that may regulate the humoral anti-HBs response. Studies with H-2 congenic and noncongenic inbred strains revealed the T-dependent humoral immune responses to the group-specific a and subtype-specific d determinants of HBsAg are regulated by gene(s) mapping to the murine MHC. The H-2q haplotype conferred high responsiveness, the H-2s,f haplotypes conferred low to nonresponsiveness, and the H-2a,b,d,k haplotypes were intermediate. Studies of H-2 recombinant strains allowed tentative mapping of regulation of the anti-a response and possibly the anti-d response to the K/I-A, I-B region of the MHC. The H-2-restricted regulation of the humoral immune response to HBsAg was circumvented by immunization with 10-fold higher HBsAg doses. These findings demonstrate a clear linkage between the murine MHC and the regulation of the immune response to specific determinants on HBsAg.

Animals↗
PubMed1995

[Effect of thyroid immune liquor on erythrocyte immune function in patients with autoimmune thyroiditis].

Thirty cases of autoimmune thyroiditis (AT) were treated with thyroid immune liquor (TIL). The results showed that the activity of erythrocyte C3b receptor and erythrocyte immune adherence enhancing factor were significantly increased, while erythrocyte immune complex and erythrocyte immune adherence inhibiting factor were decreased. The thyroid microsome-antibody and thyroid globulin-antibody were also significantly decreased. This indicates that the TIL has adjustive effect on humoral immunity and cellular immunity in patients with AT.

Adjuvants, Immunologic↗