OBJECTIVETo establish an animal model of chronic nonbacterial prostatitis (CNP) using different doses of purified prostate protein with Freund's complete adjuvant (FCA), and to investigate the relationship of the doses with the success of the model construction.

METHODSThirty male Wistar rats were divided into a control (A) and 4 experimental groups (B, C, D and E) of equal number. The latter 4 groups were given multi-loci intracutaneous injection of 1.0 ml of a 1:1 mixture of purified prostate protein at 20, 40, 60 and 80 mg/ml with Freund's complete adjuvant (FCA), and meanwhile intraperitoneally injected with 0.5 ml of pertussis-diphtheria-tetanus vaccine at 0 and 30 days. On the 45th day, the rats were sacrificed for observation of the pathomorphological changes in the prostate glands with the naked eyes and microscope.

RESULTSDifferent degrees of chronic inflammation were observed with different degrees of lymphocyte infiltration and interstitial hyperplasia in the experimental rats. More obvious changes were found in Groups C and D than in A, and even more significant in Group E (P < 0.05).

CONCLUSIONThe rat model of CNP can be successfully established by multi-loci intracutaneous injection of 1.0 ml of a 1: 1 mixture of purified prostate protein at 40 - 60 mg/ml with FCA, and simultaneously intraperitoneal injection of 0.5 ml of pertussis-diphtheria-tetanus vaccine twice within 30 days.

Animals ; Autoimmunity ; Disease Models, Animal ; Dose-Response Relationship, Immunologic ; Freund's Adjuvant ; pharmacology ; Male ; Prostatitis ; Rats ; Rats, Wistar

There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life. Most mAbs display target mediated drug disposition (TMDD), which can have significant consequences on the study designs of preclinical and clinical studies. The PK of mAb can also be influenced by anti-drug antibody (ADA) response and off-target binding, which require careful consideration during the discovery stage. mAbs are primarily absorbed through the lymphatics via convection and can be conveniently administered by the subcutaneous (sc) route in large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb can be reasonably estimated using cynomolgus monkey data and allometric scaling methods.
Absorption, Physiological ; Animals ; Antibodies, Monoclonal ; pharmacokinetics ; Dose-Response Relationship, Immunologic ; Humans ; Receptors, Fc ; metabolism ; Recombinant Fusion Proteins ; pharmacokinetics ; Tissue Distribution

OBJECTIVETo evaluate the safety, immunogenicity and fit dosage of Healive inactivated hepatitis A vaccine (HAV) in children.

METHODSA total of 85 susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled from two adjacent villages in a county. The volunteers were randomized allocated into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0 ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the same dose was given at 12th month. Local and systemic side effects were examined and seroconversion rate as well as geometric mean titers of anti-HAV antibody were tested at 3-week, 12-month after the primary dose and at 1 month after the booster dose.

RESULTSThe vaccine was well tolerated in both groups. At 21 days after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups respectively. At 12 months after the primary dose, the seroconversion rate of anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05) respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21 696 mIU/ml.

CONCLUSIONGMT of the 0, 12 month schedule was higher than other schedule after the booster vaccination. The Healive inactivated vaccine can be used for emergency vaccination. The Healive inactivated vaccine produced by Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose was considered appropriate for children.

Child ; Child, Preschool ; Dose-Response Relationship, Immunologic ; Drug Administration Schedule ; Hepatitis A ; immunology ; prevention & control ; Hepatitis A Antibodies ; analysis ; Hepatitis A Vaccines ; administration & dosage ; immunology ; Humans ; Vaccines, Inactivated ; administration & dosage ; immunology

This study evaluated the effect of Matricaria chamomilla and vaccination frequency on cattle immunization against rabies. Four groups (n = 15 /group) were treated with or without Matricaria chamomilla CH(12) and vaccinated with one or two doses of rabies vaccine (30 day interval). No effect of chamomile was found on cattle immunization against rabies; however, antibody titers were protective in cattle vaccinated twice, while 93.3% of cattle vaccinated only once had titers under 0.5 UI/ml after 60 days. In conclusion, the use of chamomile did not alter the humoral immune response in cattle, and two vaccine doses are suggested for achieving protective antibody titers.
Animals ; Antibodies, Viral/blood ; Cattle ; Dose-Response Relationship, Immunologic ; Drug Administration Schedule ; Drug Interactions ; Matricaria/*chemistry ; Plant Extracts/chemistry/*pharmacology ; Rabies Vaccines/administration & dosage/*immunology

OBJECTIVETo observe the antileukemic effect of lymphocytes from cord blood treated by CpG-oligodeoxynucleotides (CpG-ODN).

METHODSLymphocytes from cord blood were exposed to different oligodeoxynucleotides containing a panel of CpG-ODN and were cultured with K562 cells. The cytotoxic effects were detected by MTT method. Immunological markers of cord blood treated by CpG-ODN(3) which showed highest activity were measured with flow cytometry.

RESULTSDifferent CpG-motifs have different immunostimulatory activity and CpG-ODN(3) has the highest one. After treated by CpG-ODN(3), NK killing activity to K562 cells increased in a dose-dependent manner, and CD(3), CD(4), CD(19) and CD(56) increased to (60.6 +/- 7.9)%, (40.2 +/- 3.5)%, (22.4 +/- 1.9)% and (15.5 +/- 3.1)%, respectively.

CONCLUSIONCpG-ODN could reinforces the immunological competence of cord blood lymphocytes and their effects on K562 cells. This provides a new approach to reinforce the antitumor effects of cord blood.

Adjuvants, Immunologic ; pharmacology ; Antigens, CD ; blood ; Cytotoxicity, Immunologic ; Dose-Response Relationship, Drug ; Fetal Blood ; cytology ; Humans ; K562 Cells ; Leukemia ; therapy ; Lymphocytes ; drug effects ; immunology ; Oligodeoxyribonucleotides ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the immunization status of hepatitis B vaccine who were inoculated at birth, HBV infections and the vaccine booster effect in the first-year middle school students (12 - 14 years old).

METHODSA cluster, stratified simplified random sampling method was administrated. The sample size was at least 218, which was calculated by Epi Info 3.3.2 software at 53% the minimum acceptable anti-HBs positive rate and 95% confidence level. A total of 250 and 236 students participated in the infection status and booster immunization effects investigation. The HBsAg, anti-HBs and anti-HBc IgG were detected by Enzyme-linked immunosorbent assay (ELISA). HBV DNA was detected by fluorescence quantitative PCR, and the diagnostic test kit were produced respectively by ABBOTT, Diasorin and Beijing Wantai Biological Pharmacy Enterprise Co.

RESULTSFor the immunization status before booster: the positive rate of anti-HBs was 62.80% (157/250), the GMT was 73.79 IU/L; the currently HBV infection rate (HBsAg and anti-HBc positive) was 2.80% (7/250). After injection, the anti-HBs positive rate was 94.92% (224/236). Compared with the before booster results, the significant difference was observed (χ(2) = 73.92, P = 0.00). The GMT was 521.15 IU/L, comparing with the before booster results, there was significant difference (t = 15.98, P = 0.00). The anti-HBs conversion rate (from negative to positive) was 91.86% (79/86) after immune-enhancement; of which, 11 students got the second dose of booster vaccine who are no-responders after first injection, in addition 8 students got the anti-HBs.

CONCLUSIONIt is an effective method to put the first-year middle school students into the immune-enhancement program, so as to improve the immunization memory effect and avoid the loss of protective antibodies.

Adolescent ; Child ; China ; Dose-Response Relationship, Immunologic ; Female ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Antibodies ; immunology ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Humans ; Immunization, Secondary ; Immunologic Memory ; immunology ; Male ; Schools ; Students

OBJECTIVE: To evaluate the adverse reaction of standardized specific mite-allergen immunotherapy. METHOD: One hundred and fifty-two patients diagnosed by the pediatric immunotherapy center of our hospital were treated with increasing doses of standardized specific mite-allergen injection. Before and 30 minutes after treatment, the peak expiratory flow (PEF) and pulmonary function for the maximum lung ventilation function were checked, and the adverse reactions were recorded. RESULT: Six hundred and eighty-one injections were recorded. 84 injections (12.3%) caused immediate side effects, including 64 mild local adverse reactions (9.4%), 2 moderate local adverse reactions (0.3%), 18 systemic adverse reactions (2.6%) which were mild asthma, and no fatal anaphylactic shock and other serious adverse reactions were found. 50 injections (7.3%) cased delayed adverse reactions, all of which were mild local adverse reactions. The rate of immediate local adverse reactions and systemic adverse reactions in the maintenance treatment period was significantly higher than that in the initial treatment period (chi2 = 4.59, 19.82 respectively; P < 0.05, < 0.01 respectively). The rate of delayed adverse reactions was no significant differences (chi2 = 2.30; P > 0.05). The PEF change rate (-0.000 2 +/- 0.085 9) of the children at 681 injections and the MMEF change rate of the children at 109 injections (0.275 +/- 0.206) were not statistically different (t = -0.047, 1.39; P = 0.963, 0.166). CONCLUSION Standardized specific mite-allergen immunotherapy is safe for children with allergic rhinitis and/or asthma.
Adolescent ; Animals ; Asthma ; immunology ; therapy ; Child ; Child, Preschool ; Desensitization, Immunologic ; adverse effects ; standards ; Dose-Response Relationship, Immunologic ; Female ; Humans ; Hypersensitivity, Immediate ; Male ; Mites ; immunology ; Rhinitis, Allergic, Perennial ; immunology ; therapy

OBJECTIVETo evaluate the safety and immunogenicity of the Bilive(TM) combined hepatitis A and hepatitis B vaccine in healthy children.

METHODSA total of 116 healthy children aged 1 - 10 years, who, without history of hepatitis A vaccine vaccination and anti-HAV negative, had completed the full immunization of hepatitis B vaccine were recruited in city of Changzhou in Jiangsu province. The Bilive(TM) combined hepatitis A and hepatitis B vaccine was administered according to a two-dose schedule (0, 6 months). The dosage was 250 U for hepatitis A antigen and 5 microg for hepatitis B surface antigen. The potential adverse effects were observed within 72 hours after vaccination. The serum samples were collected for the testing of anti-HAV and anti-HBs at month 1, 6 and 7 after initial dose.

RESULTSThe local and systemic adverse reactions after immunization were slight and temporary. The rates of local and systemic adverse reactions were 12.1% (14/116) and 6.0% (7/116). The sero-conversion rates of HAV were from 92.9% (92/99) to 100.0% (101/101) and the geometric mean titers (GMT) ranged from 47.0 mIU/ml to 2762.3 mIU/ml 1, 6, 7 months after initial dose. The sero-protection rate of HBV was 86.1% (87/101) before vaccination and came up to 100.0% (101/101) one month after initial dose, and the GMTs of HBV were from 894.3 mIU/ml to 3314.3 mIU/ml 1, 6, 7 months after initial dose.

CONCLUSIONThe Bilive(TM) combined hepatitis A and hepatitis B vaccine has good safety and immunogenicity in healthy children who had preexisting immunity to hepatitis B virus.

Child ; Child, Preschool ; Dose-Response Relationship, Immunologic ; Female ; Hepatitis A Vaccines ; adverse effects ; immunology ; Hepatitis B Vaccines ; adverse effects ; immunology ; Humans ; Immunization Schedule ; Infant ; Male ; Vaccines, Combined ; adverse effects ; immunology

OBJECTIVETo study the mechanism of prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG).

METHODSClinical and immunological changes were observed in Lewis rats administered with dual analogue Lys262-Ala207 nasally, to compare the effects between the rats with predetermined dosage of Lys262-Ala207 and control peptides at two different time points, before the day (Group A or C) or on the day (Group B or D) of immunization with acetylcholine receptor (AChR) in complete Freud's adjuvant for 10 consecutive days. The clinical scores was evaluated for 50 days post immunization. Numbers of MNC expressing IFN-gamma, IL-4 or IL-10 and CD4+ and/or CD25+ from lymph nodes were enumerated by flow cytometry. Proliferative response, expressed as stimulation index (SI), was suppressed in response to antigen-specific stimulation in the rats receiving dual analogue, as compared with the rats receiving saline buffer only.

RESULTSGroup A and group B of Lewis rats developed EAMG with reduced severity, as compared to the control groups. Number of cells synthesizing IFN-gamma, IL-4 or IL-10 decreased, whereas numbers of CD4+CD25+ cells increased in group A and B than those in the control groups. Proliferative response was suppressed in response to antigen-specific stimulations in the rats receiving dual analogue Lys262-Ala207.

CONCLUSIONSNasal administration with a dual analogue Lys262-Ala207 at two different time points, before the day and on the day of immunization, could delay symptoms of muscular weakness in EAMG rats, which was associated with suppression of immune function in AChR antigen-specific T cells and lay a scientific foundation for treatment of human MG with nasal dual analogue.

Administration, Intranasal ; Animals ; Antibody Affinity ; Autoantibodies ; immunology ; Dose-Response Relationship, Immunologic ; Female ; Immune Tolerance ; drug effects ; Immunity, Cellular ; Immunity, Mucosal ; Lymphocyte Activation ; Myasthenia Gravis ; immunology ; prevention & control ; Nasal Mucosa ; immunology ; Rats ; Rats, Inbred Lew

OBJECTIVETo study the relationship between the immune response of anti-tetrodotoxin vaccine, including its dose-response, and to select optimal immunization dose so as to enhance antitoxic effect of the anti-tetrodotoxin vaccine.

METHODSTetrodotoxin (TTX) was coupled to Tachypleus tridentatus hemocyanin (TTH) chemically to form artificial antigen (TTX-TTH), and with which Balb/c mice were immunized. Influence of different immunization doses [100 microg as the higher (H) and 25 microg as the lower (L) dose group] on the protective effects of TTX vaccine was compared. The quality of antisera and effects of vaccine in anti-TTX poisoning were observed.

RESULTSThe sera antibody quality increased more quickly in group L than that in group H after immunization. The dose at which the half of immunized mice survived when challenged once with TTX were 16 x LD (1 LD = 13.5 microg/kg, i.p.) in group L and 11 x LD in group H. When TTX was used time and again, the half of immunized mice could tolerate as high as 40 x LD and 22 x LD of accumulated dose, and the maximum tolerable cumulated dose was 104 x LD and 90 x LD for group L and H respectively. The scheme L was better both in antibody quality and effect of protecting against TTX toxicity than that in scheme H.

CONCLUSIONSThe experimental vaccine of TTX could effectively protect animal from TTX intoxication. The lower immunization dose in this study is selected as the optimal immunization scheme.

Animals ; Antibodies ; blood ; Dose-Response Relationship, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Female ; Hemocyanins ; immunology ; Horseshoe Crabs ; Immune Sera ; immunology ; Mice ; Mice, Inbred BALB C ; Tetrodotoxin ; immunology ; toxicity ; Toxicity Tests ; Vaccination ; methods ; Vaccines ; administration & dosage ; immunology