ABSTRACT
The development of vaccines against biothreat toxins like ricin (RT) is considered an integral component of the United States national security efforts. RiVax® is a thermostable, lyophilized RT subunit vaccine adsorbed to aluminum salt adjuvant intended for use by military personnel and first responders. Phase 1 studies indicated that RiVax is safe and immunogenic, while a three dose, intramuscular vaccination regimen in non-human primates elicited protection against lethal dose RT challenge by aerosol. Here we investigated, in a mouse model, the durability of RiVax-induced antibody responses and corresponding immunity to lethal dose RT challenge. Groups of mice were subcutaneously administered 3 or 1 μg of RiVax on days 0 and 21 and challenged with 10 × LD50 RT by injection at six different intervals over the course of twelve months. Serum antibody titers and epitope-specific competition assays were determined prior to each challenge. We report that the two-dose, 3 μg regimen conferred near complete protection against RT challenge on day 35 and complete protection thereafter (challenge days 65, 95, 125, 245, and 365). The two-dose, 3 μg regimen was superior to the 1 μg regimen as revealed by slight differences in survival and morbidity scores (e.g., hypoglycemia, weight loss) on challenge days 35 and 365. In separate experiments, a single 3 μg RiVax vaccination proved only marginally effective at eliciting protective immunity to RT, underscoring the necessity of a prime-boost regimen to achieve full and long-lasting protection against RT.
IMPORTANCE Ricin toxin (RT) is a notorious biothreat, as exposure to even trace amounts via injection or inhalation can induce organ failure and death within a matter of hours. In this study, we advance the preclinical testing of a candidate RT vaccine known as RiVax®. RiVax is a recombinant non-toxic derivative of RT’s enzymatic subunit that has been evaluated for safety in Phase I clinical trials and efficacy in a variety of animal models. We demonstrate that two doses of RiVax is sufficient to protect mice from lethal dose RT challenge for up to one year. We describe kinetics and other immune parameters of the antibody response to RiVax and discuss how these immune factors may translate to humans.
