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

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 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

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

The nfa1 gene was cloned from a cDNA library of pathogenic Naegleria fowleri by immunoscreening; it consisted of 360 bp and produced a 13.1 kDa recombinant protein (rNfa1) that showed the pseudopodia-specific localization by immunocytochemistry in the previous study. Based on the idea that the pseudopodia-specific Nfa1 protein mentioned above seems to be involved in the pathogenicity of N. fowleri, we observed the effect of an anti-Nfa1 antibody on the proliferation of N. fowleri trophozoites and the cytotoxicity of N. fowleri trophozoites on the target cells. The proliferation of N. fowleri trophozoites was inhibited after being treated with an anti-Nfa1 polyclonal antibody in a dose-dependent manner for 48 hrs. By a light microscope, CHO cells co-cultured with N. fowleri trophozoites (group I) for 48 hrs showed severe morphological destruction. On the contrary, CHO cells co-cultured with N. fowleri trophozoites and anti-Nfa1 polyclonal antibody (1: 100 dilution) (group II) showed less destruction. In the LDH release assay results, group I showed 50.6% cytotoxicity, and group II showed 39.3%. Consequently, addition of an anti-Nfa1 polyclonal antibody produced a decreasing effect of in vitro cytotoxicity of N. fowleri in a dosedependent manner.
Animals ; Antibodies, Protozoan/*immunology ; Antigens, Protozoan/genetics/*immunology ; CHO Cells ; Dose-Response Relationship, Immunologic ; Female ; Hamsters ; Mice ; Mice, Inbred BALB C ; Naegleria fowleri/growth & development/immunology/*pathogenicity ; Protozoan Proteins/genetics/*immunology ; Recombinant Proteins/immunology ; Support, Non-U.S. Gov't

OBJECTIVETo evaluate the protective efficacy of plague subunit vaccine, BALB/c mice, guinea pigs and rabbits were used in this study.

METHODSGroups of mice (10 per group), guinea pigs (14 per group) and rabbits (6 per group) were immunized with F1 + rV270 vaccine, EV76 vaccine and alum adjuvant by intramuscular route, respectively. Serum antibody titres of mice, guinea pigs and rabbits were determined by ELISA and the immunized animals were challenged with 10(6) CFU of Y. pestis strain 141 at the 8th week after the primary immunization.

RESULTSThe immunized mice, guinea pigs or rabbits with subunit vaccine developed anti-F1 IgG titre of 41 587.3 +/- 2.1, 11 543.7 +/- 2.1 or 522.4 +/- 22.4 and elicited statistical anti-F1 IgG titre difference among them (F = 17.58, P < 0.01). The immunized mice, guinea pigs or rabbits with subunit vaccine had anti-rV270 IgG titre of 15 748.7 +/- 1.6, 12.6 +/- 1.4 or 1648.0 +/- 5.0 and induced statistical anti-rV270 IgG titre difference among them (F value was 16.34, P < 0.01). There was significant anti-F1 IgG titre difference among mice, guinea pigs and rabbits immunized with EV76 vaccine that developed anti-F1 IgG titre of 913.4 +/- 4.5, 937.0 +/- 2.0 or 342.0 +/- 12.0 (F = 23.67, P < 0.01), whereas the immunized mice, guinea pigs and rabbits with EV76 vaccine developed anti-rV270 IgG titre of 12.0 +/- 1.0, 447.0 +/- 10.0, 40.0 +/- 11.0 and there was no anti-rV270 IgG titre difference between them (F = 2.20, P = 0.1314). The immunized mice with subunit vaccine developed significantly higher anti-F1 IgG titres than immunized guinea pigs and rabbits (q value was 30.57 and 19.04, respectively, P < 0.01), and there were no anti-F1 IgG titre differences between the immunized guinea pigs and rabbits (q = 0.04, P = 0.8485). The immunized mice with subunit vaccine developed significantly higher anti-rV270 IgG titres than immunized guinea pigs and rabbits (q value was 27.10 and 19.49, respectively, P < 0.01), and there were no anti-rV270 IgG titre differences between the immunized guinea pigs and rabbits with the subunit vaccine (q = 0.25, P = 0.6187). The immunized mice with EV76 elicited higher anti-F1 IgG titres than immunized guinea pigs and rabbits (q value was 40.67 and 29.10, respectively, P < 0.01), whereas there was no difference of F1 IgG titer between immunized guinea pigs and rabbits (q = 0.06, P = 0.8098). The immunized mice, guinea pigs and rabbits with subunit vaccine provided 100% (10/10), 86% (12/14) and 100% (5/5) protection against 10(6) CFU Y. pestis of challenge, respectively. The immunized mice, guinea pigs and rabbits with EV76 vaccine gave 100% (6/6), 93% (13/14) and 100% (6/6) protection against 10(6) CFU Y. pestis of challenge respectively.

CONCLUSIONBALB/c mice is the best small animal model for valuation of protective efficacy of plague subunit vaccine. The guinea pigs showed a high individual variation for this purpose. The rabbits can be used as an alternative model for evaluating plague subunit vaccine.

Animals ; Antibodies, Bacterial ; blood ; Dose-Response Relationship, Immunologic ; Female ; Guinea Pigs ; Immunization ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Plague ; prevention & control ; Plague Vaccine ; immunology ; Rabbits ; Vaccines, Subunit ; immunology

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