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Vaccine. 2019 Jan 7;37(2):366-371. doi: 10.1016/j.vaccine.2018.11.045. Epub 2018 Nov 30.

Causal relationship between immunological responses and adverse reactions following vaccination.

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Kitasato Institute for Life Sciences, Laboratory of Viral Infection, 5-9-1 Shirokane Minato-ku, Tokyo 108-8641, Japan. Electronic address:


Vaccine adverse events and controversial safety issues have occurred in recent decades in Japan: aseptic meningitis following the measles-mumps-rubella combined vaccine (MMR), anaphylaxis after immunization with live virus vaccines and inactivated split influenza vaccine, an increased incidence of febrile illness following the simultaneous administration of inactivated vaccines, and chronic pain with neurological illness after immunization with the human papilloma virus vaccine (HPV). Vaccine adverse events are a matter of concern for the public as well as general practitioners; some are within the range of assumptions that adverse reactions after live attenuated vaccines are related to the nature of their parental wild-type viruses. Vaccines stimulate the innate immunity of host immunological defense mechanisms and induce the development of specific acquired immunity. Some adverse events related to autoimmune responses have been reported, such as idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis (ADEM). Although a plausible relationship was not demonstrated, the possibility of an association cannot be denied. The pathogenicity of adverse reactions was investigated for anaphylactic reactions, systemic and local reactions following vaccinations. Initial innate immune responses are essential for the development of acquired immunity and are related to adverse events from different viewpoints.


Adverse events; Adverse reaction; Anaphylaxis; Gelatin allergy; Influenza vaccine

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