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.

中文翻译：

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由耐热、冻干亚单位疫苗引起的对蓖麻毒素的持久免疫力

开发针对蓖麻毒素 (RT) 等生物威胁毒素的疫苗被认为是美国国家安全工作的一个组成部分。RiVax ^®是一种热稳定、冻干的 RT 亚单位疫苗，吸附在铝盐佐剂上，供军事人员和急救人员使用。1 期研究表明 RiVax 是安全且具有免疫原性的，而在非人类灵长类动物中进行的三剂肌肉内疫苗接种方案引发了针对气溶胶致死剂量 RT 攻击的保护。在这里，我们在小鼠模型中研究了 RiVax 诱导的抗体反应的持久性和对致死剂量 RT 攻击的相应免疫力。在第 0 天和第 21 天，给各组小鼠皮下注射 3 或 1 μg RiVax，并用 10 × LD _{50 进行}攻击在十二个月的过程中以六个不同的间隔注射 RT。在每次攻击之前确定血清抗体滴度和表位特异性竞争测定。我们报告说，两剂 3 μg 方案在第 35 天对 RT 激发几乎完全保护，然后完全保护（激发第 65、95、125、245 和 365 天）。两剂 3 μg 方案优于 1 μg 方案，这体现在攻击第 35 天和 365 天存活率和发病率评分（例如，低血糖、体重减轻）的细微差异。在单独的实验中，单次 3 μg RiVax 疫苗接种事实证明，在引发对 RT 的保护性免疫方面仅微不足道，这强调了启动-加强方案以实现对 RT 的全面和持久保护的必要性。