Time filter

Source Type

Zhu F.-C.,U.S. Center for Disease Control and Prevention | Wang J.-Z.,National Institute for Food and Drug Control | Li X.-L.,Beijing Vigoo Biological Co. | Liang Z.-L.,National Institute for Food and Drug Control | And 22 more authors.
Pediatric Infectious Disease Journal | Year: 2012

BACKGROUND: Enterovirus 71 (EV71) is highly contagious and can cause severe complications. A safe and effective vaccine is needed. We assessed the reactogenicity and immunogenicity of an inactivated, alum-adjuvanted EV71 vaccine in this study. METHODS: A randomized, double-blind, placebo-controlled clinical trial was undertaken in 360 healthy participants who were stratified into 2 age groups (6-12 and 13-60 months), and randomly allocated to receive placebo or the investigational vaccine containing 160 U, 320 U or 640 U antigen per dose by the ratio of 1:1:1:1 at days 0 and 28. Reactogenic data within 28 days after each vaccination were recorded. Blood samples were obtained on days 0, 28 and 56 for neutralizing antibody assay. RESULTS: Overall, 193 participants reported at least 1 injection-site or systemic adverse reaction with 53.3% and 54.4% participants receiving the study vaccine and placebo, respectively. Most of the reactions were mild or moderate. Three serious adverse events were observed, but none was related to vaccination. In the participants with seronegative baseline, after 2 doses all the participants receiving EV71 vaccines were seropositive and the seroconversion rates were more than 98.1%. In the participants with seropositive baseline, 1 dose induced good seroconversion rates of more than 64.3% in participants receiving EV71 vaccines. CONCLUSIONS: This study found that the inactivated EV71 vaccine was well tolerated and had good immunogenicity in healthy children and infants. A single dose induced typical booster response in the participants with a seropositive baseline, and 2 doses were needed for the immunologically naive participants. Copyright © 2012 by Lippincott Williams & Wilkins.


Chen Y.-J.,Nanjing Southeast University | Meng F.-Y.,U.S. Center for Disease Control and Prevention | Mao Q.-Y.,National Institute for Food and Drug Control | Li J.-X.,U.S. Center for Disease Control and Prevention | And 12 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

The demonstration of batch-to-batch consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This is a post-hoc analysis aimed to provide more solid evidence on the immunogenicity and consistency of 3 consecutive batches of a novel inactivated enterovirus 71 (EV71) vaccine. In total 10 245 healthy Chinese children aged 6-35 months had been recruited and randomized to receive one of 3 batches of EV71 vaccine or placebo according to a two-dose immunization schedule in a phase 3 clinical trial. Blood samples were taken just before and 28 days after vaccinations for serological tests of EV71 neutralizing antibody (NTAb) titer from the subjects. Among them, 7263 (70.9%) subjects with seronegative EV71 NTAb at baseline and the data of serological tests post-vaccination available were included for the analysis. The results showed that EV71 vaccine elicited high geometric mean titers (GMTs) of 407.0 U/mL (95% CI, 373.5-443.6) for batch 1, 468.1 U/mL (95% CI, 432.2-507.0) for batch 2, and 520.6 U/mL (95% CI, 481.2-563.3) for batch 3. The two-sided 95% confidence intervals (CIs) for the GMT ratios between each pair of vaccine batches were all within an interval of [0.67, 1.5]. Subjects who received EV71 vaccines demonstrated significant higher GMTs than those received placebos did (P < 0.001). In terms of incidence of both local and general adverse reactions, no differences were found among 3 vaccine batches and placebos. EV71 vaccine was highly immunogenic in children, and the 3 consecutive batches were well consistent. © 2014 Landes Bioscience.


Meng F.-Y.,U.S. Center for Disease Control and Prevention | Li J.-X.,U.S. Center for Disease Control and Prevention | Li X.-N.,Beijing Vigoo Biological Co. | Chu K.,U.S. Center for Disease Control and Prevention | And 5 more authors.
Human Vaccines and Immunotherapeutics | Year: 2012

In this open labeled phase 1 clinical trial with enterovirus 71 (EV71) vaccine (ClinicalTrials.gov number: NCT01267903) performed in Donghai County, Jiangsu Province, China, in January 2011. A total of 100 healthy participants, stratified by age (40 adults aged 16-22 y and 60 children aged 6-15 y), were enrolled from volunteers and sequentially received EV71 vaccines of 160U (only for children), 320U, or 640U on day 0 and 28, in a manner of dose escalation. All the participants were followed for 28 d after each shot. During the study period, 37 participants reported at least one injection-site or systemic adverse reaction. No case of grade 3 adverse reaction or serious adverse event (SAE ) was observed. Also no dose-related increase in reaction rate was noticed. Pain at injection-site and fever were the most frequently reported local and systematic reaction, respectively. The studied EV71 vaccines demonstrated acceptable tolerability and no anti-nuclear antibody (ANA) seropositive was detected pre or post vaccinations in participants. Also, no clinically significant abnormal change for the liver or kidney function indexes was found. In the according-to-protocol cohort for immunogenicity, it was observed one dose of EV71 vaccine elicited good immune response in the participants, especially for the ones with sero-positive baseline. No obvious dose-response relationship for immunogenicity was found. This study was co-founded by Beijing Vigoo Biological Co., LTD and Chinese governmental grants (2008BAI69B01 and 2009ZX10004-806). © 2012 Landes Bioscience.


Wang P.,Beijing Vigoo Biological Co. | Lin H.-T.,Beijing Vigoo Biological Co. | Jiao X.-L.,Beijing Vigoo Biological Co. | Liu M.-Y.,Beijing Vigoo Biological Co.
Chinese Journal of Biologicals | Year: 2014

Objective To develop and verify a method for determination of free polysaccharide content in group A meningococcal polysaccharide protein conjugate vaccine. Methods The phosphate content in group A meningococcal polysaccharide protein conjugate vaccine was determined by high-performance anion-exchangc chromatography with conductivity detection (HPAEC-CD) using IonPac™ AS11 Analytical (4 mm × 250 mm) column and 22 mmol/L sodium hydroxide for washing at a flow rate of 1 ml / min. A portion of 25 |i.l of samples were loaded automatically. The temperature for oxidation reaction, hydrogen peroxide concentration and time for drying were optimized, while the detection and quantitative limits of HPAEC-CD were determined, and the developed method was verified for specificity, accuracy and precision. The polysaccharide and free polysaccharide contents in three batches of bulks of polysaccharide protein conjugate A-tetanus toxoid (A-TT) were determined by the developed method, and the results were compared with those by traditional colorimetry in Chinese Pharmacopoeia (Volume III , 2010 edition). Meanwhile, the polysaccharide and free polysaccharide contents in three batches of groups A and C and three batches of groups A, C, W135 and Y meningococcal polysaccharide protein conjugate vaccines were determined. Results The condition for oxidation was optimized as treatment with 100 μl/ml hydrogen peroxide at 220 °C for 90 inin. The peak area of standard curve showed good linear relationship to the concentration of standard phosphorus at a range of 0. 1 ∼ 1 μg/ml (r = 0. 999 887). TT, C-TT, W-TT and Y-TT showed no interference to the determination result. The detection and quantitative limits of the method were 0. 007 and 0. 024 |xg / ml respectively. The recovery rate of sample in bulk of group A meningococcal polysaccharide was 97. 56% ∼ 102. 95%. The RSDs of results of reproducibility test as well as inter-assay were less than 5%. The polysaccharide and free polysaccharide contents in A-TT determined by HPAEC-CD were approximately equal to that by routine colorimetry. The polysaccharide and free polysaccharide contents in three hatches of groups A and C and three batches of groups A, C, W135 and Y meningococcal polysaccharide protein conjugate vaccines met the Requirements for Groups A and C Meningococcal Polysaccharide Protein Conjugate Vaccine (draft) and the Requirements for Groups A , C, W135 and Y Meningococctd Polysaccharide Protein Conjugate Vaccine (drift). The free polysaccharide contents in three batches of groups A and C meningococcal polysaccharide protein conjugate vaccine were 24. 31%, 23. 04% and 24. 44%, while those in three hatches of groups A, C, W135 and Y meningococcal polysaccharide protein conjugate vaccine were 19.07%, 17. 80% and 19. 46%, respectively. Conclusion The group A i>olysaccharide content, especially the free polysaccharide content in meningococcal polysaccharide protein conjugate vaccine could be determined by HPAEC-CD method after oxidation with hydrogen peroxide. This method showed high specificity, precision and accuracy, which was simple and safe, protecting the operator and the environment.


Wang X.-W.,Beijing Vigoo Biological Co. | Liu Y.,Beijing Vigoo Biological Co. | Chen J.,Beijing Vigoo Biological Co. | Jiao X.-L.,Beijing Vigoo Biological Co. | And 4 more authors.
Chinese Journal of Biologicals | Year: 2013

Objective: To purify group C meningococcal capsular polysaccharide by chromatography instead of cold phenol extraction and preliminarily evaluate the safety and immunogenicity of polysaccharide-protein conjugate prepared. Methods: Group C meningococcal capsular polysaccharide was pre-treated with mild surfactant sodium deoxycholate and purified by anion-exchange chromatography with Capto adhere and Capto DEAE columns, from which residual sodium deoxycholate was removed by desalting. The sodium deoxycholate concentration, pH value of buffer, time for pre-treatment and flow rate for anion exchange were optimized, and the developed procedure was scaled up. The batches of group C meningococcal capsular polysaccharides were purified by the developed procedure, then subjected to overall control tests according to the requirements in Chinese Pharmacopoeia(Volume III, 2010 edition), and analyzed for structure by 1H-nuclear magnetic resonance (NMR). Polysaccharide-tetanus toxoid (TT) conjugates were prepared by conjugating the polysaccharide purified by chromatography and cold phenol extraction to TT respectively, and tested for abnormal toxicity, acute toxicity in mice and immunogenicity. Results: The optimal sodium deoxycholate concentration, pH value of buffer, time for pre-treatment and flow rate for anion exchange were 1.0%, 8.0, 6 h and 2.0 ml/min. Three batches of polysaccharides purified by the developed procedure were qualified in overall control tests, while the recovery of polysaccharide was more than 70%, which was significantly higher than that purified by cold phenol extraction. The 1H-NMR spectra showed that the main peaks of polysaccharides purified by chromatography and cold phenol extraction were basically in agreement, indicating no change of structure of polysaccharide purified by chromatography. The conjugate prepared with polysaccharide purified by chromatography was qualified in abnormal toxicity test and showed good immunogenicity in mice, of which the acute toxicity test result showed no significant difference with that of polysaccharide purified by cold phenol extraction. Conclusion: Anion-exchange chromatography method for separation of foreign protein was simple to handle, time- and labor-saving and easy to be scaled up, which minimize the environmental pollution and was suitable for purification of group C meningococcal capsular polysaccharide instead of cold phenol extraction.

Loading Beijing Vigoo Biological Co. collaborators
Loading Beijing Vigoo Biological Co. collaborators