Preclinical Safety Evaluation of Vaccines

Publisher Summary The safety evaluation of vaccines is complex because composition varies from attenuated microorganisms to recombinant proteins and gene-transfer products. Vaccines act through a multistage mechanism in which the immunizing agent acts as a prodrug, while antibodies and activated lymphocytes are the actual effectors. Several potent toxicities need to be considered as a result. This chapter identifies five different categories of potential toxicological effect: Intrinsic toxicity of the test article, toxicity linked to the pharmacodynamic activity, “biological toxicity,” toxicity of contaminants and impurities, and evaluation of potential adverse reactions due to interaction between components. The chapter discusses the regulatory framework and provides an outline of proposed studies. Various toxicity studies are examined. An evaluation of adjuvants is carried out. There is a clear need for developing a scientific discipline of vaccine toxicology to provide a panel of validated methods applicable to vaccine candidates that will allow the industry to work proactively in identifying antigens and adjuvants associated with risk early in a vaccine candidate's evaluation.