21 research outputs found
Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates
BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials
In situ green synthesis of silver nanoparticles/chitosan/poly vinyl alcohol/poly ethylene glycol hydrogel nanocomposite for novel finishing of nasal tampons
Less cost by using hanging maneuver and Pringle maneuver in left lateral hepatectomy through small laparotomy wound—experience of Southern Taiwan
Relationship of Insulin-Like Growth Factors System Gene Polymorphisms with the Susceptibility and Pathological Development of Hepatocellular Carcinoma
Characterization of 3-hydroxyisobutyrate dehydrogenase, HIBADH, as a sperm-motility marker
Synthesis and biological evaluation of 2-amino-1-thiazolyl imidazoles as orally active anticancer agents
Triage of Atypical Glandular Cell by SOX1 and POU4F3 Methylation: A Taiwanese Gynecologic Oncology Group (TGOG) Study
Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury
Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia
10.1038/ng.2456Nature Genetics44121330-1335NGEN