MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
Biologicals Research Group, Research and Development Institute, Government Pharmaceutical Organization, Bangkok, Thailand.
mSphere. 2023 Apr 20;8(2):e0056422. doi: 10.1128/msphere.00564-22. Epub 2023 Feb 22.
The primary route of Zika virus (ZIKV) transmission is through the bite of an infected mosquito, when it probes the skin of a vertebrate host during a blood meal. Viral particles are injected into the bite site together with mosquito saliva and a complex mixture of other components. Some of them are known to play a key role in the augmentation of the arbovirus infection in the host, with increased viremia and/or morbidity. This vector-derived contribution to the infection is not usually considered when vaccine candidates are tested in preclinical animal models. In this study, we performed a preclinical validation of a promising ZIKV vaccine candidate in a mosquito-mouse transmission model using both Asian and African ZIKV lineages. Mice were immunized with engineered ZIKV virus-like particles and subsequently infected through the bite of ZIKV-infected Aedes aegypti mosquitoes. Despite a mild increase in viremia in mosquito-infected mice compared to those infected through traditional needle injection, the vaccine protected the animals from developing the disease and strongly reduced viremia. In addition, during peak viremia, naive mosquitoes were allowed to feed on infected vaccinated and nonvaccinated mice. Our analysis of viral titers in mosquitos showed that the vaccine was able to inhibit virus transmission from the host to the vector. Zika is a mosquito-borne viral disease, causing acute debilitating symptoms and complications in infected individuals and irreversible neuronal abnormalities in newborn children. The primary vectors of ZIKV are Aedes aegypti mosquitoes. Despite representing a significant public health burden with a widespread transmission in many regions of the world, Zika remains a neglected disease with no effective antiviral therapies or approved vaccines. It is known that components of the mosquito bite lead to an enhancement of viral infection and spread, but this aspect is often overlooked when vaccine candidates undergo preclinical validation. In this study, we included mosquitoes as viral vectors, demonstrating the ability of a promising vaccine candidate to protect animals against ZIKV infections after the bite of an infected mosquito and to also prevent its further transmission. These findings represent an additional crucial step for the development of an effective prevention tool for clinical use.
寨卡病毒（ZIKV）的主要传播途径是通过受感染蚊子的叮咬，当它在吸血时探测脊椎动物宿主的皮肤。病毒颗粒与蚊子唾液和其他成分的复杂混合物一起注入叮咬部位。其中一些已知在宿主中增强虫媒病毒感染中发挥关键作用，增加病毒血症和/或发病率。当候选疫苗在临床前动物模型中进行测试时，通常不考虑这种源自媒介的对感染的贡献。在这项研究中，我们使用亚洲和非洲 ZIKV 谱系在蚊-鼠传播模型中对一种有前途的 ZIKV 候选疫苗进行了临床前验证。小鼠用工程 ZIKV 病毒样颗粒免疫，然后通过感染 ZIKV 的埃及伊蚊叮咬感染。尽管与通过传统针注射感染的小鼠相比，感染蚊子的小鼠的病毒血症略有增加，但疫苗保护动物免受疾病侵害，并强烈降低病毒血症。此外，在病毒血症高峰期，让未感染的蚊子吸食感染的疫苗接种和未接种疫苗的小鼠。我们对蚊子中病毒滴度的分析表明，疫苗能够抑制病毒从宿主传播到媒介。寨卡病毒是一种蚊媒病毒性疾病，在感染个体中引起急性虚弱症状和并发症，并在新生儿中导致不可逆转的神经元异常。ZIKV 的主要传播媒介是埃及伊蚊。尽管在世界许多地区广泛传播，给公共卫生带来了重大负担，但寨卡病毒仍然是一种被忽视的疾病，没有有效的抗病毒疗法或批准的疫苗。已知蚊子叮咬的成分会增强病毒感染和传播，但当候选疫苗进行临床前验证时，这一方面往往被忽视。在这项研究中，我们将蚊子作为病毒载体，证明了一种有前途的候选疫苗在被感染的蚊子叮咬后能够保护动物免受 ZIKV 感染，并防止其进一步传播的能力。这些发现为开发用于临床使用的有效预防工具提供了另一个重要步骤。
