Pathological aspects of immunization of mice against influenza virus infection.

Groups of mice were immunized against influenza Ao/NWS virus by a single intranasal administration of inactivated homologous virus, by 2 intranasal doses of vaccine separated by an interval of 2 weeks, or by 2 intraperitoneal doses of the same vaccine. When subjected 2 weeks later to a standard challenge of 6 x 10(5) egg infecting units Ao/NWS virus instilled intranasally, mortality fell significantly from 64% in unimmunized mice to 39% in mice given a single intranasal dose of vaccine and to 29% in animals which received double intranasal vaccine. The best protection was conferred by double intraperitoneal immunization, after which mortality was 10%. Immunity waned with time, since the mortality of mice doubly immunized by the respiratory route and challenged 30 weeks later was 49%. Intrapulmonary lymphoid tissue developed in large amounts in a proportion of mice immunized by all methods and challenged after an interval of 2 weeks. Attention is drawn to this reaction as a possible unfavourable consequence of vaccination. There were no lesions in the lungs or central nervous system after immunization without subsequent challenge. The importance of histopathology in vaccine trials in experimental animals is emphasized by the consistently higher detection rate of lesions in lungs by histological examination than by visual inspection alone.