Yu Lan, Bai Wentao, Wu Xingan, Zhang Liang, Zhang Lei, Li Puyuan, Wang Fang, Liu Ziyu, Zhang Fanglin, Xu Zhikai
Department of Microbiology, Fourth Military Medical University, Xi'an, 710032, China.
Virol J. 2013 Oct 5;10:301. doi: 10.1186/1743-422X-10-301.
Hantaviruses cause acute hemorrhagic fever with renal syndrome (HFRS). Currently, several types of inactivated HFRS vaccines are widely used, however the limited ability of these immunogen to elicit neutralizing antibodies restricts vaccine efficacy. Development of an effective vaccine to overcome this weakness is must.
In the present study, a recombinant pseudotyped lentivirus bearing the hantaan virus (HTNV) envelope glycoproteins (GP), rLV-M, was constructed. C57BL/6 mice were immunized with the rLV-M and a series of immunological assays were conducted to determine the immunogenicity of the recombinant pseudotyped lentivirus. The humoral and cell-mediated immune responses induced by rLV-M were compared with those of the inactivated HFRS vaccine.
Indirect immunofluorescence assay (IFA) showed the rLV-M expressed target proteins in HEK-293 cells. In mice, the rLV-M efficiently induced GP-specific humoral responses and protection against HTNV infection. Furthermore, the rLV-M induced higher neutralizing antibody titers than the inactivated HFRS vaccine control.
The results indicated the potential of using a pseudotyped lentivirus as a delivery vector for a hantavirus vaccine immunogen.
汉坦病毒可引起肾综合征出血热(HFRS)。目前,几种类型的灭活HFRS疫苗被广泛使用,然而这些免疫原诱导中和抗体的能力有限,限制了疫苗的效力。开发一种有效的疫苗来克服这一弱点是必要的。
在本研究中,构建了携带汉滩病毒(HTNV)包膜糖蛋白(GP)的重组假型慢病毒rLV-M。用rLV-M免疫C57BL/6小鼠,并进行一系列免疫学检测以确定重组假型慢病毒的免疫原性。将rLV-M诱导的体液免疫和细胞介导的免疫反应与灭活HFRS疫苗的免疫反应进行比较。
间接免疫荧光法(IFA)显示rLV-M在HEK-293细胞中表达靶蛋白。在小鼠中,rLV-M有效地诱导了GP特异性体液反应,并对HTNV感染具有保护作用。此外,rLV-M诱导的中和抗体滴度高于灭活HFRS疫苗对照组。
结果表明使用假型慢病毒作为汉坦病毒疫苗免疫原的递送载体具有潜力。