Evaluation of an Engineered Zika Virus-Like Particle Vaccine Candidate in a Mosquito-Mouse Transmission Model.
Evaluation of an Engineered Zika Virus-Like Particle Vaccine Candidate in a Mosquito-Mouse Transmission Model.
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寨卡病毒（ZIKV）的主要传播途径是被感染的伊蚊叮咬，当它在吸食血液时探测脊椎动物宿主的皮肤时。病毒颗粒与蚊子唾液和其他成分的复杂混合物一起注射到叮咬部位。其中一些已知在增加宿主虫媒病毒感染中起关键作用，增加病毒血症和/或发病率。在临床前动物模型中测试候选疫苗时，通常不考虑这种媒介衍生的感染贡献。在这项研究中，我们在使用亚洲和非洲寨卡病毒谱系的蚊子-小鼠传播模型中对一种有希望的寨卡病毒候选疫苗进行了临床前验证。用改造过的寨卡病毒样颗粒免疫小鼠，随后通过感染寨卡病毒的埃及伊蚊叮咬感染小鼠。尽管与通过传统针头注射感染的小鼠相比，蚊子感染小鼠的病毒血症略有增加，但疫苗保护了动物免受疾病的侵袭，并大大减少了病毒血症。此外，在病毒血症高峰期，允许未接种疫苗和未接种疫苗的感染小鼠为食的蚊子。我们对蚊子体内病毒滴度的分析表明，该疫苗能够抑制病毒从宿主向媒介的传播。寨卡病毒是一种蚊子传播的病毒性疾病，在感染者中引起急性衰弱症状和并发症，并在新生儿中引起不可逆的神经异常。寨卡病毒的主要媒介是埃及伊蚊。尽管寨卡病毒在世界许多地区广泛传播，构成了重大的公共卫生负担，但它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。众所周知，蚊子叮咬的成分会导致病毒感染和传播的增强，但在候选疫苗进行临床前验证时，这方面往往被忽视。在这项研究中，我们将蚊子作为病毒载体，证明了一种有希望的候选疫苗能够在被感染的蚊子叮咬后保护动物免受ZIKV感染，并防止其进一步传播。这些发现为开发临床使用的有效预防工具又迈出了关键的一步。
The primary route of Zika virus (ZIKV) transmission is through the bite of an infected Aedes 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. IMPORTANCE 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.
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影响因子：
3.8
作者：
Dowall SD;Graham VA;Rayner E;Hunter L;Atkinson B;Pearson G;Dennis M;Hewson R
通讯作者：
Hewson R
影响因子：
56.3
作者：
Ades, A. E.;Thorne, Claire;Giaquinto, Carlo
通讯作者：
Giaquinto, Carlo
影响因子：
56.9
作者：
Aubry, Fabien;Dabo, Stephanie;Lambrechts, Louis
通讯作者：
Lambrechts, Louis
影响因子：
16.6
作者：
Aubry F;Jacobs S;Darmuzey M;Lequime S;Delang L;Fontaine A;Jupatanakul N;Miot EF;Dabo S;Manet C;Montagutelli X;Baidaliuk A;Gámbaro F;Simon-Lorière E;Gilsoul M;Romero-Vivas CM;Cao-Lormeau VM;Jarman RG;Diagne CT;Faye O;Faye O;Sall AA;Neyts J;Nguyen L;Kaptein SJF;Lambrechts L
通讯作者：
Lambrechts L
影响因子：
32.4
作者：
Pingen M;Bryden SR;Pondeville E;Schnettler E;Kohl A;Merits A;Fazakerley JK;Graham GJ;McKimmie CS
通讯作者：
McKimmie CS