Virology Division, USA Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, USA.
SAB Biotherapeutics Inc., Sioux Falls, South Dakota, USA.
mBio. 2024 Oct 16;15(10):e0160024. doi: 10.1128/mbio.01600-24. Epub 2024 Sep 11.
Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s).
This candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world's most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.
汉坦病毒是由啮齿动物传播的病毒，会导致感染人类的严重疾病。在新世界，主要的汉坦病毒包括安第斯病毒（ANDV）和辛诺波病毒（SNV），导致汉坦病毒肺综合征。在旧世界，主要的汉坦病毒包括汉坦病毒（HTNV）和普马拉病毒（PUUV），导致肾综合征出血热。在这里，我们生产了一种泛汉坦病毒治疗药物（SAB-163），由转染色体牛（TcB）的血浆中纯化的完全人免疫球蛋白组成，转染色体牛接种了编码 ANDV、SNV、HTNV 和 PUUV 主要糖蛋白的汉坦病毒 DNA 质粒。SAB-163 对四种目标汉坦病毒具有强大的中和抗体（PRNT50>200,000），并对几种其他异型汉坦病毒具有交叉中和作用。在 10mg/kg 的剂量下，SAB-163 在叙利亚仓鼠中可在治疗后 70 天内达到生物利用度，半衰期为 10-15 天。在相同剂量下，SAB-163 在接触前 1 天或接触后 5 天给药，可保护所有仓鼠免受 ANDV 引起的致命疾病。在较高剂量下，即使在第 6 天，也能获得部分但显著的保护。当在 HTNV、PUUV 和 SNV 感染模型中给药时，SAB-163 也可在接触前 1 天或最多 3 天后保护仓鼠。这种泛汉坦病毒治疗药物很有吸引力，因为它是完全人类的、多靶向的、安全的，在 4°C 下稳定，并且在动物模型中有效。SAB-163 在 GLP 人类组织结合研究和 GLP 兔毒性研究中进行了安全性评估，剂量为 365 和 730mg/kg，已获得新药临床试验（IND）许可。
该候选多克隆人 IgG 产品是使用合成基因疫苗和转基因奶牛生产的。在经历了 cGMP 生产、GLP 安全性测试和动物疗效测试后，SAB-163 是世界上除恢复期人血浆外最先进的抗汉坦病毒抗体类医疗对策。重要的是，SAB-163 针对四大洲最常见的汉坦病毒。
