Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies.
Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies.
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DOI：
10.1016/j.vaccine.2021.11.003
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发表时间：
2021-12-20
期刊：
影响因子：
5.5
通讯作者：
Fikrig E
中科院分区：
文献类型：
--
作者：
Matias J;Kurokawa C;Sajid A;Narasimhan S;Arora G;Diktas H;Lynn GE;DePonte K;Pardi N;Valenzuela JG;Weissman D;Fikrig E
暴露于肩突硬蜱蜱多次侵染的豚鼠对蜱产生获得性抗性，也称为蜱免疫。重症监护有助于蜱虫免疫的肩胛唾液成分可能是多因素的。一种抑制Xa因子的抗凝剂，名为Salp 14，存在于蜱唾液中，与部分蜱免疫有关。蜱叮咬自然释放蜱唾液蛋白进入脊椎动物宿主数天，这表明抗原递送模式可能影响蜱免疫的发生。因此，我们利用Salp 14作为模型抗原，使用mRNA脂质纳米颗粒（LNP）、质粒DNA或重组蛋白平台来检查蜱免疫。与DNA或蛋白质免疫相比，含有salp 14的mRNA-LNP疫苗接种在蜱虫攻击后在蜱虫叮咬部位引起红斑，这发生得更早，并且更明显。与蜱免疫相关的体液和细胞应答针对Salp 14蛋白羧基末端的25个氨基酸区域，如通过抗体应答和皮肤测试测定。这项研究表明，抗原递送模型，也称为疫苗平台，可以影响豚鼠蜱免疫的发生。mRNA-LNP可能有助于在蜱叮咬部位引起红斑，这是获得性蜱抗性的最重要的早期标志之一。含有蜱基因的mRNA-LNP是用于开发可以潜在地预防选定的蜱传播疾病的疫苗的有用平台。
Guinea pigs exposed to multiple infestations with Ixodes scapularis ticks develop acquired resistance to ticks, which is also known as tick immunity. The I. scapularis salivary components that contribute to tick immunity are likely multifactorial. An anticoagulant that inhibits factor Xa, named Salp14, is present in tick saliva and is associated with partial tick immunity. A tick bite naturally releases tick saliva proteins into the vertebrate host for several days, which suggests that the mode of antigen delivery may influence the genesis of tick immunity. We therefore utilized Salp14 as a model antigen to examine tick immunity using mRNA lipid nanoparticles (LNPs), plasmid DNA, or recombinant protein platforms. salp14 containing mRNA-LNPs vaccination elicited erythema at the tick bite site after tick challenge that occurred earlier, and that was more pronounced, compared with DNA or protein immunizations. Humoral and cellular responses associated with tick immunity were directed towards a 25 amino acid region of Salp14 at the carboxy terminus of the protein, as determined by antibody responses and skin-testing assays. This study demonstrates that the model of antigen delivery, also known as the vaccine platform, can influence the genesis of tick immunity in guinea pigs. mRNA-LNPs may be useful in helping to elicit erythema at the tick bite site, one of the most important early hallmarks of acquired tick resistance. mRNA-LNPs containing tick genes is a useful platform for the development of vaccines that can potentially prevent selected tick-borne diseases.
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DOI：
10.1016/j.jbc.2021.100865
发表时间：
2021-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Denisov SS;Ippel JH;Castoldi E;Mans BJ;Hackeng TM;Dijkgraaf I
通讯作者：
Dijkgraaf I
影响因子：
3.2
作者：
Narasimhan, Sukanya;Kurokawa, Cheyne;Fikrig, Erol
通讯作者：
Fikrig, Erol
影响因子：
2.1
作者：
MATHER, TN;TELFORD, SR;SPIELMAN, A
通讯作者：
SPIELMAN, A
影响因子：
2.4
作者：
Jongejan, F;Uilenberg, G
通讯作者：
Uilenberg, G
影响因子：
4.8
作者：
Kotsyfakis, Michalis;Sa-Nunes, Anderson;Ribeiro, Jose M. C.
通讯作者：
Ribeiro, Jose M. C.