Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Vaccine. 2024 Oct 24;42(24):126304. doi: 10.1016/j.vaccine.2024.126304. Epub 2024 Sep 5.
Repeated exposure of animals to Ixodes scapularis ticks can result in acquired tick resistance (ATR). The first manifestation of ATR is erythema at the tick bite site, however, the specific peptide targets and mechanisms associated with this early aspect of ATR are not understood. In this study, we immunized guinea pigs with a lipid nanoparticle containing the mRNA encoding 25 amino acids in the carboxyl terminus of Salp14 (Salp14-C mRNA-LNP), an I. scapularis salivary protein. The animals produced high titers of IgG directed at the carboxyl terminus of Salp14. Guinea pigs immunized with Salp14-C mRNA-LNP and then exposed to I. scapularis, developed erythema at the tick bite site. Transcriptomics of the skin of guinea pigs at the I. scapularis bite sites elucidated selected pathways, including histamine activation, that are associated with the development of erythema. The study demonstrates that an mRNA vaccine encoding a small peptide can induce the initial phase of ATR in guinea pigs.
动物反复接触扁虱可导致获得性抗蜱（ATR）。ATR 的第一个表现是蜱叮咬部位的红斑，然而，与 ATR 这一早期阶段相关的特定肽靶标和机制尚不清楚。在这项研究中，我们用含有编码 Salp14 羧基末端 25 个氨基酸的 mRNA 的脂质纳米颗粒（Salp14-C mRNA-LNP）对豚鼠进行免疫，Salp14 是一种扁虱唾液蛋白。这些动物产生了针对 Salp14 羧基末端的高滴度 IgG。用 Salp14-C mRNA-LNP 免疫的豚鼠然后暴露于扁虱，在蜱叮咬部位出现红斑。对 I. scapularis 叮咬部位豚鼠皮肤的转录组学分析阐明了与红斑发展相关的选定途径，包括组胺激活。该研究表明，编码小肽的 mRNA 疫苗可诱导豚鼠 ATR 的初始阶段。
