1.Establishment of a nonbacterial prostatitis model in rats using the autoimmune method: a dose-effect study.
Guo-Hong SONG ; Wen-Yu LI ; Chen ZHANG ; Ying-Jia LIU ; Ying DING
National Journal of Andrology 2011;17(7):586-590
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
2.Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins.
Protein & Cell 2018;9(1):15-32
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
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Animals
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Antibodies, Monoclonal
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pharmacokinetics
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Dose-Response Relationship, Immunologic
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Humans
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Receptors, Fc
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metabolism
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Recombinant Fusion Proteins
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pharmacokinetics
;
Tissue Distribution
3.Efficiency of Matricaria chamomilla CH(12) and number of doses of rabies vaccine on the humoral immune response in cattle.
Luis Souza DE SOUZA REIS ; Neuza Maria FRAZATTI-GALLINA ; Rosana DE LIMA PAOLI ; Rogerio GIUFFRIDA ; Avelino ALBAS ; Eunice OBA ; Paulo Eduardo PARDO
Journal of Veterinary Science 2008;9(4):433-435
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
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Antibodies, Viral/blood
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Cattle
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Dose-Response Relationship, Immunologic
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Drug Administration Schedule
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Drug Interactions
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Matricaria/*chemistry
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Plant Extracts/chemistry/*pharmacology
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Rabies Vaccines/administration & dosage/*immunology
4.The study on the 0, 12 month vaccination schedule' of Healive inactivated hepatitis A vaccine in children.
Yin-hai REN ; Jiang-ting CHEN ; Wen-ting WU ; Xue-jie GONG ; Yu-cheng ZHANG ; Wei-hua XUE ; Yi-feng REN ; Lian-jun HAN ; Wen-xue KANG ; Sheng-ping LI ; Chong-bai LIU
Chinese Journal of Epidemiology 2003;24(11):1013-1015
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
5.Study of antileukemic effect of CpG-oligodeoxynucleotides treated cord blood.
Chun-yan CHEN ; Ji-hui JIA ; Xiang-lin PAN ; Ya-bin ZHOU ; Wei-ming ZHAO
Chinese Journal of Hematology 2004;25(1):13-16
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
6.Current status of hepatitis B immunization and strengthened immune memory among first-year middle school students in Tianjin.
Ai-lan SHAN ; Chao LI ; Wei-shen WU ; Hai-yan HE ; Yong LIU ; Peng LIU ; Xiao-hua XIE
Chinese Journal of Preventive Medicine 2010;44(6):531-534
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
7.Study on safty of standardized specific mite-allergen immunotherapy to children with allergic rhinitis and/or asthma.
Yabin WU ; Zhen LONG ; Yang HUANG ; Xuanzhao HUANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2011;25(14):641-644
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
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Animals
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Asthma
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immunology
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therapy
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Child
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Child, Preschool
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Desensitization, Immunologic
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adverse effects
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standards
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Dose-Response Relationship, Immunologic
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Female
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Humans
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Hypersensitivity, Immediate
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Male
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Mites
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immunology
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Rhinitis, Allergic, Perennial
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immunology
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therapy
8.Decreasing effect of an anti-Nfa1 polyclonal antibody on the in vitro cytotoxicity of pathogenic Naegleria fowleri.
Seok Ryoul JEONG ; Su Yeon KANG ; Sang Chul LEE ; Kyoung Ju SONG ; Kyung il IM ; Ho Joon SHIN
The Korean Journal of Parasitology 2004;42(1):35-40
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
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Antibodies, Protozoan/*immunology
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Antigens, Protozoan/genetics/*immunology
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CHO Cells
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Dose-Response Relationship, Immunologic
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Female
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Hamsters
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Mice
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Mice, Inbred BALB C
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Naegleria fowleri/growth & development/immunology/*pathogenicity
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Protozoan Proteins/genetics/*immunology
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Recombinant Proteins/immunology
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Support, Non-U.S. Gov't
9.Modulatory effects of chitosan adipate on the T and B lymphocyte subsets in mice.
Bozena OBMINSKA-MRUKOWICZ ; Marianna SZCZYPKA ; Bartosz GAWEDA
Journal of Veterinary Science 2006;7(2):157-160
This study examined the subsets of T lymphocytes in the thymus, spleen and mesenteric lymph nodes as well as the subsets of B lymphocytes in the spleen and mesenteric lymph nodes in mice administered chitosan adipate (20 mg/kg) intraperitoneally once or four times at 24 h intervals. The results showed that chitosan adipate decreased the percentage of immature CD4+CD8+ thymic T cells and increased the percentage of mature CD4+ and CD8+ thymocytes. The most significant stimulating effect was observed after four injections. A single exposure to chitosan adipate increased the percentage of CD4+ mesenteric lymph node cells, but four injections of the drug increased the percentage of CD4+ and CD8+ mesenteric lymph node cells. Chitosan adipate had no effect on the subset of splenic T cells. In contrast, chitosan adipate administered either once or four times increased the percentage of CD19+ splenocytes but had no effect on the percentage of CD19+ mesenteric lymph node cells. Overall, chitosan adipate induces the maturation and differentiation of thymocytes, and regulates the number of B splenic cells and lymph node T cells irrespective of the number of doses.
Animals
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B-Lymphocyte Subsets/*drug effects/metabolism
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Chitosan/*analogs&derivatives/*pharmacology
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Dose-Response Relationship, Drug
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Female
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Immunologic Factors/pharmacology
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Lymphoid Tissue/drug effects/metabolism
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Male
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Mice
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Mice, Inbred BALB C
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T-Lymphocyte Subsets/*drug effects/metabolism
10.Protective efficacy of vaccination with Neospora caninum multiple recombinant antigens against experimental Neospora caninum infection.
Jung Hwa CHO ; Woo Suk CHUNG ; Kyoung Ju SONG ; Byoung Kuk NA ; Seung Won KANG ; Chul Yong SONG ; Tong Soo KIM
The Korean Journal of Parasitology 2005;43(1):19-25
Protective efficacy of vaccination with Neospora caninum multiple recombinant antigens against N. caninum infection was evaluated in vitro and in vivo. Two major immunodominant surface antigens (NcSAG1 and NcSRS2) and two dense granule proteins (NcDG1 and NcDG2) of N. caninum tachyzoites were expressed in E. coli, respectively. An in vitro neutralization assay using polyclonal antisera raised against each recombinant antigen showed inhibitory effects on the invasion of N. caninum tachyzoites into host cells. Separate groups of gerbils were immunized with the purified recombinant proteins singly or in combinations and animals were then challenged with N. caninum. Following these experimental challenges, the protective efficacy of each vaccination was determined by assessing animal survival rate. All experimental groups showed protective effects of different degrees against experimental infection. The highest protection efficacy was observed for combined vaccination with NcSRS2 and NcDG1. Our results indicate that combined vaccination with the N. caninum recombinant antigens, NcSRS2 and NcDG1, induces the highest protective effect against N. caninum infection in vitro and in vivo.
Animals
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Antibodies, Protozoan/immunology
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Antigens, Protozoan/immunology
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Cercopithecus aethiops
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Coccidiosis/prevention & control
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Dose-Response Relationship, Immunologic
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Gene Expression
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Gerbillinae
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Neospora/*immunology
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Protozoan Vaccines/*immunology
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Research Support, Non-U.S. Gov't
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Vaccines, Synthetic/immunology
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Vero Cells