Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes
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DOI:
10.1371/journal.pntd.0007806
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发表时间:
2019-10-01
影响因子:
3.8
通讯作者:
Arca, Bruno
Arca, Bruno
中科院分区:
医学2区
文献类型:
--
作者:
Buezo Montero, Sara;Gabrieli, Paolo;Arca, Bruno

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研究背景伊蚊是与公众健康密切相关的虫媒病毒性疾病的传播媒介。最近爆发的登革热、寨卡病毒、基孔肯雅热以及白纹伊蚊在全球的迅速传播,突出表明需要改进病媒监测和控制。蚊子唾液抗原的宿主抗体反应正在成为一个相关的额外的工具,直接评估媒介-宿主接触,监测控制干预措施的效力和评估arboviral transmission.Methodology/principal findingsGroups的风险四只BALB/c小鼠进行免疫接种暴露于叮咬的白纹伊蚊或埃及伊蚊。Ae. albopictus(al 34 k2)和Ae.埃及伊蚊(ae 34 k2)的重组表达,并与Ae.通过B细胞表位预测软件设计白纹伊蚊唾液肽。在暴露的小鼠中测量对唾液腺提取物、肽、al 34 k2和ae 34 k2的IgG应答。al 34 k2和ae 34 k2两者,具有一些个体和抗原特异性变异,在免疫小鼠中引起清楚可检测的抗体应答。值得注意的是,这两种orthopathy蛋白显示出非常低的免疫交叉反应性,这表明它们最终可能被开发为宿主暴露的物种特异性标记物。在对Ae超免疫的单个人类供体中证实了a134 k2的免疫原性和对ae 34 k2的有限免疫交叉反应性。结论:白纹伊蚊叮咬后,白纹伊蚊唾液中的蛋白质含量明显增加,白纹伊蚊唾液中的蛋白质含量明显增加。albopictus或Ae.埃及伊蚊在小鼠中分别引起对a134 k2或ae 34 k2的物种特异性IgG应答。当然需要更深入地了解抗体反应的持续时间,并在人类接触伊蚊的自然条件下进行验证。然而,我们的研究结果指出,al 34 k2唾液蛋白作为一个有前途的潜在候选人的发展免疫测定,以评估人类暴露于Ae。白纹伊蚊这将是在建立血清学工具箱以同时评估人类接触伊蚊病媒及其传播的病原体方面向前迈出的一步。
BackgroundAedes mosquitoes are vectors of arboviral diseases of great relevance for public health. The recent outbreaks of dengue, Zika, chikungunya and the rapid worldwide spreading of Aedes albopictus emphasize the need for improvement of vector surveillance and control. Host antibody response to mosquito salivary antigens is emerging as a relevant additional tool to directly assess vector-host contact, monitor efficacy of control interventions and evaluate risk of arboviral transmission.Methodology/principal findingsGroups of four BALB/c mice were immunized by exposure to bites of either Aedes albopictus or Aedes aegypti. The 34k2 salivary proteins from Ae. albopictus (al34k2) and Ae. aegypti (ae34k2) were expressed in recombinant form and Ae. albopictus salivary peptides were designed through B-cell epitopes prediction software. IgG responses to salivary gland extracts, peptides, al34k2 and ae34k2 were measured in exposed mice. Both al34k2 and ae34k2, with some individual and antigen-specific variation, elicited a clearly detectable antibody response in immunized mice. Remarkably, the two orthologous proteins showed very low level of immune cross-reactivity, suggesting they may eventually be developed as species-specific markers of host exposure. The al34k2 immunogenicity and the limited immune cross-reactivity to ae34k2 were confirmed in a single human donor hyperimmune to Ae. albopictus saliva.Conclusions/significanceOur study shows that exposure to bites of Ae. albopictus or Ae. aegypti evokes in mice species-specific IgG responses to al34k2 or ae34k2, respectively. Deeper understanding of duration of antibody response and validation in natural conditions of human exposure to Aedes mosquitoes are certainly needed. However, our findings point to the al34k2 salivary protein as a promising potential candidate for the development of immunoassays to evaluate human exposure to Ae. albopictus. This would be a step forward in the establishment of a serological toolbox for the simultaneous assessment of human exposure to Aedes vectors and the pathogens they transmit.