ABSTRACT

Coxsackievirus A16 (CV-A16) is a major causative pathogen of hand, foot, and mouth diseases (HFMDs). The licensed HFMD vaccine targets EV-A71 without cross-protection against CV-A16. Thus, a CV-A16 vaccine is needed. In this study, the immunogenicity and protective efficacy of a live attenuated CV-A16 candidate, K168-8Ac, were evaluated in a rhesus monkey model. Four passages of this strain (P35, P50, P60, and P70) were administered to monkeys, and its protective effect was identified. The immunized monkeys were clinically asymptomatic, except for slight fever. Weak viraemia was observed, and two doses of vaccination were found to significantly reduce virus shedding. High levels of antibody responses were observed (1:1024–1:2048), along with a significant increase in plasma IL-8. The I.M. group showed a much stronger humoural immunity. Pathological damage was detected mainly in lung tissues, although thalamus, spinal cord, lymph nodes, and livers were involved. After the viral challenge, it was found that two doses of vaccine reduced virus shedding, and the degree of lung damage and the number of organs involved decreased as the passage number increased. Overall, a robust immune response and partial protection against CV-A16, triggered by the K168-8Ac strain, were demonstrated. This study provides valuable data for CV-A16 vaccine development.

摘要

柯萨奇病毒A16（CV-A16）是手足口病（HFMD）的主要病原体。许可的HFMD疫苗靶向EV-A71，而没有针对CV-A16的交叉保护。因此，需要CV-A16疫苗。在这项研究中，在恒河猴模型中评估了减毒活CV-A16候选株K168-8Ac的免疫原性和保护功效。对猴子施用了四代该菌株（P35，P50，P60和P70），并确定了其保护作用。除轻微发烧外，免疫的猴子在临床上无症状。观察到微弱的病毒血症，发现两剂疫苗可以显着减少病毒的脱落。观察到高水平的抗体反应（1：1024-1：2048），以及血浆IL-8的显着增加。IM组表现出更强的体液免疫力。尽管涉及丘脑，脊髓，淋巴结和肝脏，但主要在肺组织中检测到病理损害。病毒攻击后，发现两剂疫苗减少了病毒的脱落，并且随着传代次数的增加，肺部损伤的程度和所涉及的器官数量减少了。总体而言，证明了由K168-8Ac菌株引发的强大的免疫应答和对CV-A16的部分保护。这项研究为CV-A16疫苗开发提供了有价值的数据。证实了由K168-8Ac菌株引发的强大的免疫反应和对CV-A16的部分保护。这项研究为CV-A16疫苗的开发提供了有价值的数据。证实了由K168-8Ac菌株引发的强大的免疫反应和对CV-A16的部分保护。这项研究为CV-A16疫苗的开发提供了有价值的数据。