Li Zhuo, Gabbard Jon D, Johnson Scott, Dlugolenski Daniel, Phan Shannon, Tompkins S Mark, He Biao
Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, GA, 30602, United States of America.
PLoS One. 2015 Mar 24;10(3):e0120355. doi: 10.1371/journal.pone.0120355. eCollection 2015.
H7N9 has caused fatal infections in humans. A safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. Parainfluenza virus 5 (PIV5), an avirulent paramyxovirus, is a promising vaccine vector. In this work, we generated a recombinant PIV5 expressing the HA gene of H7N9 (PIV5-H7) and tested its efficacy against infection with influenza virus A/Anhui/1/2013 (H7N9) in mice and guinea pigs. PIV5-H7 protected the mice against lethal H7N9 challenge. Interestingly, the protection did not require antibody since PIV5-H7 protected JhD mice that do not produce antibody against lethal H7N9 challenge. Furthermore, transfer of anti-H7 serum did not protect mice against H7N9 challenge. PIV5-H7 generated high HAI titers in guinea pigs, however it did not protect against H7N9 infection or transmission. Intriguingly, immunization of guinea pigs with PIV5-H7 and PIV5 expressing NP of influenza A virus H5N1 (PIV5-NP) conferred protection against H7N9 infection and transmission. Thus, we have obtained a H7N9 vaccine that protected both mice and guinea pigs against lethal H7N9 challenge and infection respectively.
H7N9已导致人类出现致命感染。一种安全有效的疫苗是预防该病毒在人群中大规模暴发的最佳方式。副流感病毒5型(PIV5)是一种无毒的副黏病毒,是一种很有前景的疫苗载体。在本研究中,我们构建了一种表达H7N9血凝素基因(HA)的重组PIV5(PIV5-H7),并在小鼠和豚鼠中测试了其对甲型流感病毒A/安徽/1/2013(H7N9)感染的效力。PIV5-H7保护小鼠免受致死剂量H7N9的攻击。有趣的是,这种保护作用并不依赖抗体,因为PIV5-H7能保护JhD小鼠(一种不产生针对致死剂量H7N9攻击的抗体的小鼠)。此外,注射抗H7血清并不能保护小鼠免受H7N9的攻击。PIV5-H7在豚鼠中产生了高血凝抑制(HAI)效价,然而它并不能预防H7N9感染或传播。有趣的是,用PIV5-H7和表达甲型流感病毒H5N1核蛋白(NP)的PIV5免疫豚鼠可使其免受H7N9感染和传播。因此,我们获得了一种H7N9疫苗,该疫苗分别保护小鼠和豚鼠免受致死剂量H7N9的攻击和感染。