Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program. Evaluation of the Passive Protection Against Five Serotypes of Botulinum Toxin Provided by Botulinum Human Immune Globulin in an Animal Model

摘要

Pentavalent (ABCDE) botulinum toxoid vaccine is intended for use as a prophylactic measure to protect combat troops against the lethal effects of botulinum toxins A-E, a group of toxins considered to be a serious biological warfare threat. To adequately assess the level of protection afforded by this vaccine, efficacy against an inhalation challenge must be established for all five toxin serotypes. Due to the inherent dangers of these toxins and the exceedingly rare incidence of botulism, efficacy cannot be established in traditional phase 3 clinical trials. This study proposes to indirectly measure efficacy by establishing a serological correlate that is indicative of efficacy. An FDA Advisory Panel, in addressing efficacy issues for bacterial vaccines and toxoids, made the following statement (Federal Register 1985): 'For diseases in which immunity depends upon specific antibodies which either neutralize toxin or which opsonize bacteria and lead to their prompt destruction within phagocytes, induction of such antibodies correlates well with protection, and the measurement of such antibodies may reflect efficacy quite faithfully.' Humoral immunity can effectively be assessed by measuring neutralizing botulinum antibodies in serum using a mouse bioassay. The objective of this study is to establish toxin-neutralizing antibody levels as a serological correlate for efficacy.