Vetnuus | September 2024 17 The first attempts to develop a tissue culture vaccine were made by Kissling17 in 1958 and Fenje18 in 1960. Both investigators used primary hamster kidney (PHK) cells for the production of the RABV. In the early 1960s, staff at the Wistar Institute in Philadelphia, Pennsylvania, developed a human diploid cell vaccine (HDCV) using the WI-38 human diploid cell line for viral propagation, which avoids side effects such as animal protein allergies produced by primary tissue culture.19 HDCV contains concentrated and purified viruses, and the immune response in experimental animals and humans is much better than that of DEV, neonatal mouse brain, and adult animal brain tissue vaccines.20 Although HDCV has good immunogenicity, its production costs and price are high. Therefore, the world has been striving to produce rabies vaccines at lower costs while achieving or exceeding the efficacy, safety, and immunogenicity levels achieved by HDCV. A rabies vaccine developed by Sanofi Pasteur in Europe and many developing countries based on virus cultivation in Vero cells (African green monkey kidney cells) has been licensed.21 A purified Vero cell rabies vaccine (PVRV) for human use has also been launched and used by multiple factories in India (e.g. Bharat Biotechnology, Wockhardt, and the Institute of Human Bioproducts) and China (e.g. Chengdu Biotechnology, Wuhan Institute of Bioproducts, Liaoning Yisheng Biopharmaceutical Co., Ltd., and Liaoning Chengda Biotechnology Co., Ltd.,).12 During the production of PVRV, Vero cells can grow and infect Article Vaccine name Manufacturers Type Substrates Viral strains Remarks Locations Nerve Tissue Vaccines Pasteur Many, through the mid20th century Partially inactivated by drying Rabbit spinal cord Pasteur fixed strain Contained adult animal nerve tissue and residual live RABV NLU Fermi Many, throughout the 20th century Phenolised, live virus Sheep, goat, or rabbit brains CVS Contains adult nerve tissue and residual live RABV NLU, except in Ethiopia Semple Many, throughout the 20th century Phenol inactivated Sheep, goat, or rabbit brains PV-11 Contained adult animal nerve tissue NLU Avian Embryo Vaccines PDEV Several (e.g., Berna, Zydus Cadila) β-propiolactone inactivated (BPL) Duck embryo PM Purified by ultracentrifugation Europe, worldwide DEV Several (e.g., Eli Lilly) BPL Duck embryo PM Allergy to avian antigens NLU HEP Lederle Laboratories Attenuated RABV Chick embryo cells PM Poorly immunogenic compared to other biologics NLU Cell Culture Vaccines HDCV Several (e.g., Chengdu Kanghua, Sanofi Pasteur, Serum Institute of India) BPL Human cultured fibroblasts PM Expensive, standard for rabies vaccine United States, Europe, and worldwide RVA Local (e.g., Michigan Department of Health, Bioport) BPL Foetal rhesus cell culture CVS-122 Fewer allergic reactions United States (NLU) FBKC Local (e.g., Pasteur Institute) BPL Foetal bovine kidney cell PV-31 Concentrated and purified by zonal centrifugation Several countries in Europe, Africa (NLU) PHKCV Local Typically formalininactivated Primary Syrian hamster kidney cell culture SAD, Ag Used historically in the People’s Republic of China and the former USSR China, Russia PCECV Several (e.g., Bavarian Nordic, Bharat Biotech) BPL Chick embryo cell culture PM Purified by ultracentrifugation United States, Europe, and worldwide PVRV Several (e.g., Bharat Biotech, Indian Immunologicals, Sanofi Pasteur) BPL Vero cell line PV206, CTN- 1, aG Purified by ultracentrifugation Europe, and worldwide DEV, duck embryo vaccine; HEP, Flury high egg passage vaccine; HDCV, human diploid cell vaccine; NLU, no longer used; PCECV, primary chick embryo cell vaccine; PDEV, purified DEV; PHKCV, primary hamster kidney cell vaccine; PVRV, purified Vero rabies vaccine; RVA, rhesus cell rabies vaccine. Table 1. Major past and present rabies vaccines for human prophylaxis. >>> 18
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