Mechanisms of protective immunogenicity of microbial vaccines: effects of cyclophosphamide pretreatment in Venezuelan encephalitis, Q fever and tularaemia.

Administration of high-dose (250 mg/kg) cyclophosphamide (CY) to guinea-pigs and mice 3 days prior to immunization with inactivated vaccine derived from Venezuelan encephalitis virus (VE), Coxiella burnetii and Francisella tularensis resulted in accentuated and prolonged delayed-type hypersensitivity (DTH) and in vitro cellular immunity (CMI) to specific antigen. Humoral antibody were either absent or significantly lower in CY-pretreated animals compared to immunized non-pretreated controls. CY pretreatments precluded protection in the VE virus model, suggesting that resistance is related to antibody. In the Q fever model, the protective immunogenicity of vaccine was preserved or increased by CY pretreatment suggesting that cell-mediated immunity is the important factor. In the tularaemia bacterial system, there was a complex effect of CY pretreatment on the low-grade protection afforded by killed vaccine against virulent infection. These findings suggest that the inability of killed vaccines to induce high-grade resistance against tularaemia and Q fever may be due in part to a suppressive B cell response which is eliminated by CY. These studies have given useful information on the relative significance of components of the specific immune response and may lead to an increased understanding of the mechanisms of action of vaccines and adjuvants.