Sullivan Nancy J, Geisbert Thomas W, Geisbert Joan B, Xu Ling, Yang Zhi-Yong, Roederer Mario, Koup Richard A, Jahrling Peter B, Nabel Gary J
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 40, Room 4502, MSC 3005, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA.
Nature. 2003 Aug 7;424(6949):681-4. doi: 10.1038/nature01876.
Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses.
控制高致死性埃博拉病毒疫情是一项严峻的公共卫生挑战。尽管一种实验性疫苗已成功保护非人灵长类动物免受疾病侵害,但完成免疫接种需要六个多月时间,这使得在急性疫情期间进行限制变得不切实际。在此,我们报告了在非人灵长类动物中加速接种埃博拉病毒疫苗的进展。与DNA初免和腺病毒载体(ADV)加强免疫相比,用编码埃博拉糖蛋白(GP)的腺病毒载体免疫诱导抗体反应的速度更快,但反应强度较低。为了确定这种更早的免疫反应是否仍能预防疾病,在用ADV-GP和核蛋白(NP)载体接种疫苗后,用埃博拉病毒对食蟹猴进行攻击。保护效果非常显著,且与埃博拉特异性CD8(+) T细胞和抗体反应的产生相关。即使动物只用ADV-GP/NP免疫一次并在28天后受到攻击,它们对低剂量或高剂量病毒的攻击仍具有抵抗力。这种加速疫苗提供了一种可能有助于限制埃博拉疫情传播的干预措施,并且适用于其他病毒。