Japanese encephalitis virus is the causative agent of an acute inflammatory illness of the central nervous system found throughout eastern Asia. A formalin activated, mouse-brain derived Japanese encephalitis virus vaccine has been developed. A report of severe urticarial reactions associated with immunization with Japanese encephalitis virus vaccine was published in the Lancet. The rate of severe side-effects was reported to be 0.04%. The description of the adverse reactions was similar to allergic reactions seen when booster doses of rabies vaccine were given. The Centers for Disease Control were invited to participate in an investigation of the patients. A case control study is planned. We will obtain sera for testing for IgE antibodies by the RAST test. The patients will be skin tested with the vaccine lot associated with the reaction, another vaccine lot produced using an earlier manufacturing method, and a recently prepared lot. We have reviewed the vaccine manufacturing scheme to identify steps in manufacture of components of the vaccine that may be allergenic. We will be examining sera for antibodies to gelatin and protamine sulfate. If the allergen can be identified then the manufacturing process will be reviewed and alternatives will be sought to exclude the allergen. If the cause of the allergic reactions cannot be removed or cannot be defined, a warning indicating the possibility of this adverse reaction will be added to the package insert.
