使用mRNA和rVSV平台的同源和异源疫苗接种方案可诱导针对发热伴血小板减少综合征病毒糖蛋白的强效免疫反应。

Homologous and Heterologous Vaccination Regimens with mRNA and rVSV Platforms Induce Potent Immune Responses Against SFTSV Glycoprotein.

作者信息

Manzoni Tomaz B, Westover Jonna B, Lundgreen Kendall A, Hicks Philip D, Petch Raegan J, Ort Jordan T, Weissman Drew, Fan Steven H Y, Hensley Scott E, Pardi Norbert, Gowen Brian B, Bates Paul

机构信息

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA.

出版信息

Viruses. 2025 Aug 8;17(8):1095. doi: 10.3390/v17081095.

BACKGROUND

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic bunyavirus with a high case-fatality ratio for which there is no approved vaccine. Studies have assessed different vaccine technologies. However, few studies have yet assessed the immunogenicity of heterologous prime-boost regimens.

METHODS

Here, we compare a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA-based vaccine encoding the SFTSV glycoproteins, Gn and Gc, to our recently described recombinant VSV SFTSV (rVSV-SFTSV) vaccine in single dose, homologous, and heterologous prime-boost regimens in mice.

RESULTS

We show that all regimens protect from pathogenic SFTSV challenge and elicit strong long-lasting antibody responses. Furthermore, strong cellular immunity is elicited by mRNA-LNP immunizations and by heterologous immunization with an rVSV-SFTSV prime and mRNA-LNP boost. Cellular responses robustly polarized towards a type 1 response, characterized by high levels of IFNγ, TNFα, and IL-2. Immunization with mRNA led to a mixed type 1/type 2 immune response, as determined by antibody isotypes IgG1 and IgG2c. We found that homologous immunization leads to stronger antibody responses while heterologous immunization drives a slightly stronger cellular response.

CONCLUSIONS

Taken together, the vaccine platforms described here represent strong vaccine candidates for further development.

背景

严重发热伴血小板减少综合征病毒（SFTSV）是一种高致病性布尼亚病毒，病死率高，目前尚无获批疫苗。已有研究评估了不同的疫苗技术。然而，很少有研究评估异源初免-加强免疫方案的免疫原性。

方法

在此，我们将一种脂质纳米颗粒（LNP）包裹的、编码SFTSV糖蛋白Gn和Gc的核苷修饰mRNA疫苗，与我们最近描述的重组水泡性口炎病毒SFTSV（rVSV-SFTSV）疫苗，在小鼠中进行单剂量、同源和异源初免-加强免疫方案的比较。

结果

我们发现，所有方案均能保护小鼠免受致病性SFTSV攻击，并引发强烈且持久的抗体反应。此外，mRNA-LNP免疫以及rVSV-SFTSV初免和mRNA-LNP加强的异源免疫可引发强烈的细胞免疫。细胞反应强烈偏向1型反应，其特征是高水平的IFNγ、TNFα和IL-2。通过抗体亚型IgG1和IgG2c测定，mRNA免疫导致1/2混合型免疫反应。我们发现，同源免疫导致更强的抗体反应，而异源免疫驱动稍强的细胞反应。