Immunologic Approach to the Identification and Development of Vaccines to VariousToxins

摘要

We have used the protein synthesis inhibitor ricin and the sodium channel blockersaxitoxin (STX) as model toxic agents to investigate the feasibility of developing safe and effective vaccines against the in vivo toxicity of biological and chemical toxins. Because of their extreme in vivo toxicity, they can not be utilized as immunogens to elicit protective immunity. Thus, we have focused on the anti-idiotype and synthetic peptide-based approaches in our vaccine development strategy. A number of anti-idiotype reagents were produced, some of which were demonstrated to elicit in vivo protective immunity against ricin intoxication. In addition, recent results suggested that a cyclic ricin A peptide homologous to residues 88-112 provided some protection against ricin toxicity in vivo. The results obtained thus far with the STX system were less encouraging. Although anti-idiotype reagents produced were capable of inducing specific and systemic anti-STX antibody responses in vivo, the immunity elicited did not provide significant protection against STX toxicity. However, some delay in the time between STX administration and death was observed with some of the anti-idiotype reagents.