Department of Internal Medicine, Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands; Amsterdam Multidisciplinary Lyme borreliosis Center, Academic Medical Center, Amsterdam, The Netherlands.
Department of Internal Medicine, Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Vaccine. 2023 Mar 17;41(12):1951-1960. doi: 10.1016/j.vaccine.2023.02.003. Epub 2023 Feb 14.
Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis, are transmitted by Ixodes ticks. Tick saliva proteins are instrumental for survival of both the vector and spirochete and have been investigated as targets for vaccine targeting the vector. In Europe, the main vector for Lyme borreliosis is Ixodes ricinus, which predominantly transmits Borrelia afzelii. We here investigated the differential production of I. ricinus tick saliva proteins in response to feeding and B. afzelii infection.
Label-free Quantitative Proteomics and Progenesis QI software was used to identify, compare, and select tick salivary gland proteins differentially produced during tick feeding and in response to B. afzelii infection. Tick saliva proteins were selected for validation, recombinantly expressed and used in both mouse and guinea pig vaccination and tick-challenge studies.
We identified 870 I. ricinus proteins from which 68 were overrepresented upon 24-hours of feeding and B. afzelii infection. Selected tick proteins were successfully validated by confirming their expression at the RNA and native protein level in independent tick pools. When used in a recombinant vaccine formulation, these tick proteins significantly reduced the post-engorgement weights of I. ricinus nymphs in two experimental animal models. Despite the reduced ability of ticks to feed on vaccinated animals, we observed efficient transmission of B. afzelii to the murine host.
Using quantitative proteomics, we identified differential protein production in I. ricinus salivary glands in response to B. afzelii infection and different feeding conditions. These results provide novel insights into the process of I. ricinus feeding and B. afzelii transmission and revealed novel candidates for an anti-tick vaccine.
伯氏疏螺旋体(Borrelia burgdorferi sensu lato)是莱姆病的病原体,通过硬蜱传播。蜱唾液蛋白对于宿主和螺旋体的生存都至关重要,并且已被研究作为针对传播媒介的疫苗靶点。在欧洲,莱姆病的主要传播媒介是蓖子硬蜱(Ixodes ricinus),主要传播伯氏疏螺旋体(Borrelia afzelii)。本研究调查了硬蜱在进食和感染伯氏疏螺旋体(Borrelia afzelii)时,唾液蛋白的差异产生情况。
使用无标记定量蛋白质组学和 Progenesis QI 软件,鉴定、比较和选择硬蜱在进食和感染伯氏疏螺旋体(Borrelia afzelii)时差异产生的唾液腺蛋白。选择蜱唾液蛋白进行验证、重组表达,并用于小鼠和豚鼠的疫苗接种和蜱挑战研究。
从 870 个蓖子硬蜱蛋白中鉴定出 68 个在 24 小时进食和感染伯氏疏螺旋体(Borrelia afzelii)时过度表达。通过在独立的蜱池中确认 RNA 和天然蛋白水平上的表达,成功验证了选定的蜱蛋白。当用于重组疫苗配方时,这些蜱蛋白显著降低了两种实验动物模型中硬蜱若虫的饱食后体重。尽管接种疫苗的动物的蜱虫进食能力降低,但我们观察到伯氏疏螺旋体(Borrelia afzelii)向宿主的有效传播。
使用定量蛋白质组学,我们鉴定了硬蜱唾液腺对伯氏疏螺旋体(Borrelia afzelii)感染和不同进食条件的差异蛋白产生。这些结果为硬蜱进食和伯氏疏螺旋体(Borrelia afzelii)传播的过程提供了新的见解,并揭示了抗蜱疫苗的新候选物。