Department of Internal Medicine, Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center, Amsterdam, Netherlands.
Front Immunol. 2021 Feb 25;12:615011. doi: 10.3389/fimmu.2021.615011. eCollection 2021.
sensu lato (sl) is the causative agent of Lyme borreliosis. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines. DNA tattoo vaccination with strain PKo OspC in mice has proven to be fully protective against syringe challenge and induces a favorable humoral immunity compared to recombinant protein vaccination. Alternatively, several recombinant protein vaccines based on tick proteins have shown promising effect in tick-bite infection models. In this study, we evaluated the efficacy of DNA vaccines against OspC or tick antigens in a tick-bite infection model.
We vaccinated C3H/HeN mice with OspC using a codon-optimized DNA vaccine or with recombinant protein. We challenged these mice with sensu stricto (ss)-infected nymphs. Subsequently, we vaccinated C3H/HeN mice with DNA vaccines coding for tick proteins for which recombinant protein vaccines have previously resulted in interference with tick feeding and/or transmission: Salp15, tHRF, TSLPI, and Tix-5. These mice were also challenged with ss infected nymphs.
DNA tattoo and recombinant OspC vaccination both induced total IgG responses. cultures and DNA loads of skin and bladder remained negative in the mice vaccinated with OspC DNA vaccination, except for one culture. DNA vaccines against tick antigens Salp15 and Tix-5 induced IgG responses, while those against tHRF and TSLPI barely induced any IgG response. In addition, cultures, and DNA loads from mice tattooed with DNA vaccines against tick proteins TSLPI, Salp15, tHRF, and Tix-5 were all positive.
A DNA tattoo vaccine against OspC induced high specific IgG titers and provided near total protection against ss infection by tick challenge. In contrast, DNA tattoo vaccines against tick proteins TSLPI, Salp15, tHRF, and Tix-5 induced low to moderate IgG titers and did not provide protection. Therefore, DNA tattoo vaccination does not seem a suitable vaccine strategy to identify, or screen for, tick antigens for anti-tick vaccines. However, DNA tattoo vaccination is a straightforward and effective vaccination platform to assess novel sl antigen candidates in a relevant tick challenge model.
广义传播因子（sl）是莱姆病的病原体。目前尚无针对莱姆病的人类疫苗，大多数研究集中在重组蛋白疫苗上。在小鼠中用 株 PKo OspC 进行 DNA 纹身疫苗接种已被证明对注射器挑战具有完全保护作用，并诱导比重组蛋白疫苗接种更有利的体液免疫。或者，几种基于蜱蛋白的重组蛋白疫苗已在蜱叮咬感染模型中显示出有希望的效果。在这项研究中，我们评估了针对 OspC 或蜱抗原的 DNA 疫苗在蜱叮咬感染模型中的功效。
我们使用密码子优化的 DNA 疫苗或重组蛋白对 C3H/HeN 小鼠进行 OspC 疫苗接种。我们用感染了 sl 的感染的若虫挑战这些小鼠。随后，我们用编码以前的重组蛋白疫苗已导致干扰蜱摄食和/或传播的蜱蛋白的 DNA 疫苗对 C3H/HeN 小鼠进行疫苗接种：Salp15、tHRF、TSLPI 和 Tix-5。这些小鼠也用感染了 sl 的感染的若虫进行了挑战。
DNA 纹身和重组 OspC 疫苗接种均诱导总 IgG 反应。除一个培养物外，用 OspC DNA 疫苗接种的小鼠的皮肤和膀胱的 培养物和 DNA 载量均为阴性。针对蜱抗原 Salp15 和 Tix-5 的 DNA 疫苗诱导 IgG 反应，而针对 tHRF 和 TSLPI 的 DNA 疫苗几乎未诱导任何 IgG 反应。此外，用针对蜱蛋白 TSLPI、Salp15、tHRF 和 Tix-5 的 DNA 疫苗接种的小鼠的 培养物和 DNA 载量均为阳性。
针对 OspC 的 DNA 纹身疫苗诱导高特异性 IgG 滴度，并通过蜱挑战提供对 sl 感染的近乎完全保护。相比之下，针对蜱蛋白 TSLPI、Salp15、tHRF 和 Tix-5 的 DNA 纹身疫苗诱导低至中度 IgG 滴度，并且不能提供保护。因此，DNA 纹身疫苗接种似乎不是识别或筛选抗蜱疫苗的蜱抗原的合适疫苗策略。然而，DNA 纹身疫苗接种是一种简单有效的疫苗接种平台，可在相关的蜱挑战模型中评估新型 sl 抗原候选物。
