title: Vero-cell rabies vaccine produced using serum-free medium.
abstract: A new rabies vaccine was developed from Vero cells adhered to microcarriers, cultivated in a bioreactor in serum-free medium and infected with the PV/VERO-Paris rabies virus strain. The viral suspensions were concentrated by tangential filtration, purified by chromatography and inactivated with beta-propiolactone. In immunogenicity studies performed in mice immunized with three doses of the new vaccine (seven batches) and the commercial Verorab and HDCV, mean titers of neutralizing antibodies of 10.3-34.6, 6.54 and 9.36 IU/ml were found, respectively. The vaccine presented stability during 14 months at 2-8 degrees C, 30 days at 37 degrees C and 8 h at 45 degrees C. The use of serum-free medium facilitated the downstream process leading to residual cellular DNA values <22.8 pg per dose of vaccine in all produced batches. The effective immunogenicity induced in mice by this vaccine, the degree of purity of the product, the high antigen yield and the reduction of the cost of the product due to the virus production and purification processes, makes this technology very important for countries where rabies presents a great public health problem.
authors.affiliation: Laboratório de Raiva, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 S. Paulo, Brasil. galinajr@uol.com.br
authors.forename: Neuza M
authors.initials: NM
authors.lastname: Frazatti-Gallina
authors.forename: Regina M
authors.initials: RM
authors.lastname: Mourão-Fuches
authors.forename: Rosana L
authors.initials: RL
authors.lastname: Paoli
authors.forename: Maria L N
authors.initials: ML
authors.lastname: Silva
authors.forename: Cosue
authors.initials: C
authors.lastname: Miyaki
authors.forename: Elizabeth J G
authors.initials: EJ
authors.lastname: Valentini
authors.forename: Isaias
authors.initials: I
authors.lastname: Raw
authors.forename: Hisako G
authors.initials: HG
authors.lastname: Higashi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019149:Bioreactors; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free; D004355:Drug Stability; D051379:Mice; D008863:Microspheres; D009500:Neutralization Tests; D011819:Rabies Vaccines / Q000096:biosynthesis* / Q000276:immunology*; D011820:Rabies virus / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D013696:Temperature; D013997:Time Factors; D014709:Vero Cells; D014776:Virus Cultivation; D038301:Virus Inactivation
chemical_list: D000914:Antibodies, Viral; D016895:Culture Media, Serum-Free; D011819:Rabies Vaccines