State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, People's Republic of China.
Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Vaccine. 2023 Nov 30;41(49):7482-7490. doi: 10.1016/j.vaccine.2023.11.017. Epub 2023 Nov 11.
Hantaan virus (HTNV, Orthohantavirus hantanensae species, Hantaviridae family) is the main etiological agent responsible for hemorrhagic fever with renal syndrome (HFRS). The novel HTNV may pose a potential danger to the control and prevention of HFRS in China, which highlights the importance of vaccine development in public health management. In previous studies, our laboratory discovered and successfully isolated a new HTNV strain, HV004 strain, from Apodemus agrarius captured in an epidemic area in Hubei, China.
An initial biological and pathogenicity characterization of HTNV 76-118 (standard train), HV114 strain (a clinical isolate from Hubei province in 1986), and the novel isolate HV004 strain from the epidemic areas of Hubei province were performed in susceptible cells and in vivo. An experimental HV004 strain inactivated vaccine was prepared, and its corresponding immunogenicity was analyzed in BALB/c mice.
HV004 strain had a similar but higher pathogenicity than HTNV 76-118 and HV114 in suckling mice. A subcutaneous vaccination (s.c.) with the inactivated HTNV vaccine adjuvanted with aluminum, followed by a challenge intraperitoneally with 10 FFU/ml HTNV, afforded full protection against an HTNV challenge. All immunized mice in every group elicited serum neutralizing antibodies with increasing dosages, which may protect mice from HTNV infection. A dose-dependent stimulation index of splenocytes was also observed in immunized mice. The percentage of IFN-γ-producing CD3CD8 T cells was significantly higher in the spleens of immunized mice than in those of control mice.
These findings suggest that the inactivated HTNV vaccine may stimulate mice to produce high levels of antibodies with neutralization activity and elicit specific anti-HTNV humoral and cellular immune responses in BALB/c mice against the prevalent strain of HTNV in south central China.
汉坦病毒（HTNV，正汉坦病毒属汉坦病毒科）是引起肾综合征出血热（HFRS）的主要病原体。新型 HTNV 可能对中国 HFRS 的防控构成潜在威胁，这凸显了疫苗开发在公共卫生管理中的重要性。在之前的研究中，我们实验室从中国湖北疫区捕获的黑线姬鼠中发现并成功分离出一种新的 HTNV 株 HV004 株。
在易感细胞和体内对 HTNV 76-118（标准株）、HV114 株（1986 年湖北分离株）和来自湖北疫区的新型分离株 HV004 株进行初步的生物学和致病性特征分析。制备了实验性 HV004 株灭活疫苗，并在 BALB/c 小鼠中分析其免疫原性。
HV004 株在乳鼠中的致病性与 HTNV 76-118 和 HV114 株相似，但更高。用铝佐剂皮下接种（s.c.）灭活 HTNV 疫苗，然后腹腔内用 10 FFU/ml HTNV 进行攻击，可完全保护免受 HTNV 攻击。每个组的所有免疫小鼠均随着剂量的增加产生血清中和抗体，这可能保护小鼠免受 HTNV 感染。免疫小鼠的脾细胞刺激指数也呈剂量依赖性。与对照组相比，免疫小鼠脾脏中 IFN-γ 产生的 CD3CD8 T 细胞的百分比明显更高。
这些发现表明，灭活的 HTNV 疫苗可能刺激小鼠产生高水平具有中和活性的抗体，并在 BALB/c 小鼠中引发针对中国中南部流行 HTNV 株的特异性抗 HTNV 体液和细胞免疫反应。
