International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14926-31. doi: 10.1073/pnas.1112149108. Epub 2011 Aug 23.
Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can be lethal to humans and animals and results in major losses in the livestock industry. RVF is exotic to the United States; however, mosquito species native to this region can serve as biological vectors for the virus. Thus, accidental or malicious introduction of this virus could result in RVFV becoming endemic in North America. Such an event would likely lead to significant morbidity and mortality in humans, and devastating economic effects on the livestock industry. Currently, there are no licensed vaccines for RVF that are both safe and efficacious. To address this issue, we developed two recombinant RVFV vaccines using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine, vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-γ binding protein, insertional inactivation of the thymidine kinase gene, and expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcγ, is identical to the first and also expresses the human IFN-γ gene to enhance safety. Both vaccines are extremely safe; neither resulted in weight loss nor death in severe combined immunodeficient mice, and pock lesions were smaller in baboons compared with the controls. Furthermore, both vaccines induced protective levels of antibody titers in vaccinated mice and baboons. Mice were protected from lethal RVFV challenge. Thus, we have developed two safe and efficacious recombinant vaccines for RVF.
裂谷热（RVF）是一种在非洲和阿拉伯半岛流行的人畜共患病，由高传染性裂谷热病毒（RVFV）引起，对人类和动物具有致命性，并导致畜牧业的重大损失。裂谷热对美国来说是外来的；然而，本地区的蚊子种类可以作为该病毒的生物载体。因此，这种病毒的意外或恶意引入可能导致裂谷热病毒在北美流行。这种情况很可能导致人类发病率和死亡率显著上升，并对畜牧业造成毁灭性的经济影响。目前，尚无既安全又有效的 RVF 许可疫苗。为了解决这个问题，我们使用牛痘病毒（VACV）作为载体，开发了两种重组 RVFV 疫苗，用于畜牧业。第一种疫苗 vCOGnGc 通过删除编码 IFN-γ 结合蛋白的 VACV 基因、插入失活胸苷激酶基因以及表达 RVFV 糖蛋白 Gn 和 Gc 而减弱。第二种疫苗 vCOGnGcγ 与第一种疫苗相同，还表达了人 IFN-γ 基因以提高安全性。这两种疫苗都非常安全；在严重联合免疫缺陷小鼠中，它们既没有导致体重减轻，也没有导致死亡，而且在狒狒中，痘疱病变比对照组小。此外，这两种疫苗在接种疫苗的小鼠和狒狒中均诱导了保护性抗体滴度。小鼠免受致死性 RVFV 挑战的保护。因此，我们已经开发出两种安全有效的 RVF 重组疫苗。
