交叉反应性抗体可预防小鼠感染致死性蜱传脑炎病毒。

Cross-reactive antibodies against Langat virus protect mice from lethal tick-borne encephalitis virus infection.

机构信息

Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

Department of Pathology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

出版信息

Front Immunol. 2023 Feb 28;14:1134371. doi: 10.3389/fimmu.2023.1134371. eCollection 2023.

INTRODUCTION

Naturally attenuated Langat virus (LGTV) and highly pathogenic tick-borne encephalitis virus (TBEV) share antigenically similar viral proteins and are grouped together in the same flavivirus serocomplex. In the early 1970s, this has encouraged the usage of LGTV as a potential live attenuated vaccine against tick-borne encephalitis (TBE) until cases of encephalitis were reported among vaccinees. Previously, we have shown in a mouse model that immunity induced against LGTV protects mice against lethal TBEV challenge infection. However, the immune correlates of this protection have not been studied.

METHODS

We used the strategy of adoptive transfer of either serum or T cells from LGTV infected mice into naïve recipient mice and challenged them with lethal dose of TBEV.

RESULTS

We show that mouse infection with LGTV induced both cross-reactive antibodies and T cells against TBEV. To identify correlates of protection, Monitoring the disease progression in these mice for 16 days post infection, showed that serum from LGTV infected mice efficiently protected from developing severe disease. On the other hand, adoptive transfer of T cells from LGTV infected mice failed to provide protection. Histopathological investigation of infected brains suggested a possible role of microglia and T cells in inflammatory processes within the brain.

DISCUSSION

Our data provide key information regarding the immune correlates of protection induced by LGTV infection of mice which may help design better vaccines against TBEV.

简介

自然衰减的兰加特病毒（LGTV）和高致病性蜱传脑炎病毒（TBEV）具有抗原上相似的病毒蛋白，并被归为同一黄病毒血清复合物。在 20 世纪 70 年代早期，这促使人们使用 LGTV 作为针对蜱传脑炎（TBE）的潜在减毒活疫苗，直到疫苗接种者中出现脑炎病例。以前，我们在小鼠模型中表明，针对 LGTV 诱导的免疫可保护小鼠免受致死性 TBEV 挑战感染。然而，这种保护的免疫相关性尚未得到研究。

方法

我们使用将来自 LGTV 感染小鼠的血清或 T 细胞过继转移到 naive 受体小鼠中，并对其用致死剂量的 TBEV 进行攻击的策略。

结果

我们表明，LGTV 感染诱导了针对 TBEV 的交叉反应性抗体和 T 细胞。为了确定保护相关性，监测这些小鼠在感染后 16 天的疾病进展情况表明，LGTV 感染小鼠的血清能够有效地防止发生严重疾病。另一方面，从 LGTV 感染小鼠过继转移 T 细胞未能提供保护。感染大脑的组织病理学研究表明，小胶质细胞和 T 细胞可能在大脑内的炎症过程中发挥作用。