PRODUCTION OF VACCINES

摘要

A vaccine comprises antigens derived from myxoviruses inactivated by a process which comprises contacting the viruses in aqueous suspension at pH 6-8 in the presence of at least about 0.05% w/v. of a non-ionic hydrophilic surface active agent with a fully or partially chlorinated, or chlorinated and fluorinated C1-5 hydrocarbon, other than CHCl3, which is liquid at 15-25 DEG C. Specified myxoviruses are M. influenzae-A, B, and C, M. parainfluenzae-1, 2, 3, and 4, M. multiformae, M. pestigalli, M. parotidis, measles virus, distemper virus, rinder-pest virus, and respiratory syncytical virus. The non-ionic surface active agent may be a polyoxyethylene sorbitan mono-oleate or another polyoxyalkylene ether of partial lauric, palmitic, stearic or oleic acid esters. Specified halogenated hydrocarbons are CCl4, CHCl= CCl2, CCl2=CCl2, CFCl2.CClF2, CCl3.CH2.CCl3 and Cl2.C=C.Cl-C.Cl=C.Cl2. Any strain of the selected virus may be used. The virus may be cultivated on chick embryo or monkey kidney tissue cultures, stable diploid cell line culture or, where appropriate, in embryonated hens' eggs. The tissue culture fluid or harvested allantoic fluid is clarified and the virus therein is inactivated by contact with the above organic solvent. The organic solvent is subsequently removed, leaving an aqueous suspension containing inactivated fragmented virus particles, i.e. the primary vaccine. Stabilizers, e.g. polyvinyl pyrrolidone or dextran, and protamine sulphate, may be added. The primary vaccine may be purified or concentrated, e.g. by adsorbing the fragments of inactivated virus on to aluminium oxide or hydroxide or an aluminium salt (e.g. phosphate or alum) substantially isoluble at pH 6-8. Alternatively, a soluble aluminium salt may be added in solution to the primary vaccine and alum precipitated therefrom by the addition of an appropriate potassium salt and adjustment of pH to the required value. The adsorbate may be separated and resuspended in a saline solution buffered to pH 6.0-8.0. The purified or concentrated vaccine may be mixed with other vaccines, or the aluminium salt, oxide or hydroxide may be used to adsorb other materials having different antigenicity.