Chromatographically Purified Vero Cell Rabies Vaccine(CPRV)

Chromatographically purified Vero cell rabies vaccine (CPRV) using perfusion microcarrier technology.

Rabies vaccine was routinely produced by culturing rabies virus in roller-bottles, but the limited surface area and culture condition, roller-bottle protocol produce low-density of cells, labor intensive, ease of contamination, therefore, it is hard to produce the vaccine products with good quality [2, 3].

Since the emerging of the micro-carrier bioreactor technology, many institutions throughout the world have done an extensive researches on the application of this technology in vaccine production, including batch culture, fed-batch culture, and semi-continuous feeding culture. However, the combination of micro-carrier bioreactor and perfusion culture has not yet been investigated. Perfusion culture is a dynamic culture system, which constantly feeds in the fresh medium and pumps out waste medium without disturb the cells in the bioreactor, thus providing the continuous nutritious environment during the cell culture. By controlling the perfusion speed supply enough nutrients, and to remove the toxic metabolites, the culture environment maintains a stable condition with low inhibition activity, therefore, it not only increase the cell density, but also improve the refinement procedure [1].

Liaoning Cheng  Da Biotechnology Co., Ltd  (CDBIO) brought the  technology of cell cultured by bioreactor with microcarriers from BARI  Consultants, USA to successfully  manufacture  the rabies vaccine for human use after  assimilation, absorption, and innovation in June, 2002 [1, 2, 5]. It is proved that the product has good tolerability, high immunogenicity, and good potency after the observation of clinical trials, and the post marketing surveillance data for about 220,000 people in 20 provinces after coming into the market [1, 2].

The CPRV is a lyophilized of inactivated, purified rabies virus obtained by infection of a continuous Vero cell line propagated on micro-carriers in bioreactor.

The perfusion bioreactor technology can improve the density of cell growth. The virus bulk is concentrated by ultrafiltration, inactivated by β-propiolactone, and purified by chromatography [1, 2, 4]. The CPRV shows satisfactory clinical safety and immunogenicity for human pre- and post-exposure prophylaxis of rabies [1, 2, 4].


1. Cha Li, et al. Preparation of Rabies Vaccine for Human Use by Cell Culture in Bioreactor. Chin J Biologicals May 2006, Vol. 19 No.3

2. Pengcheng Yu, et al. Production and evaluation of a chromatographically purified Vero cell rabies vaccine in China using microcarrier technology. Human Vaccines & Immunotherapeutics, 2012, 8:9, 1230-5.

3. Microcarrier Cell Culture Principles and Methods, GE Healthcare

4. Tantawichien, et al. Safety and immunogenicity of chromatographically purified Vero cell rabies vaccine for intradermal pre- and post-exposure rabies prophylaxis. Expert Rev. Vaccines 2014. 13(12), 1593–1601.

5. Bari Consultants LLC,