Cryogel vaccines effectively induce immune responses independent of proximity to the draining lymph nodes.
Cryogel vaccines effectively induce immune responses independent of proximity to the draining lymph nodes.
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Cryogel 疫苗可有效诱导免疫反应，而与是否接近引流淋巴结无关。
DOI：
10.1016/j.biomaterials.2021.121329
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发表时间：
2022
期刊：
影响因子：
14
通讯作者：
Mooney,DavidJ
中科院分区：
文献类型：
--
作者：
Najibi,AlexanderJ;Shih,Ting-Yu;Mooney,DavidJ
传统疫苗的接种地点会影响免疫反应和产生的效力。基于冷冻凝胶的癌症疫苗通常注射在腹股沟淋巴结（iLN）附近，原位募集和激活树突状细胞（DC），诱导DC归巢到iLN，并产生针对几种鼠癌症模型的有效抗肿瘤免疫力。然而，考虑到支架疫苗位点的高度重要性，冷冻凝胶疫苗接种到引流LN的距离是否影响DC归巢和下游抗原特异性免疫的动力学尚不清楚。我们假设在iLN附近接种疫苗将导致DC更快速地运输到iLN，从而诱导更快和更强的免疫应答。在此，在iLN附近或远端向小鼠注射抗卵清蛋白的冷冻凝胶疫苗，并评估所得DC运输动力学、T细胞表型、抗原特异性T细胞和体液应答以及在表达卵清蛋白的肿瘤模型中的预防功效。Cryogel疫苗诱导有效的、持久的抗原特异性免疫应答，而与与iLN的距离无关，在DC运输动力学、卵清蛋白特异性T细胞和抗体应答或预防功效方面没有显著差异。此外，当在肿瘤附近注射冷冻凝胶时，DC运输和活化状态不受影响。这些结果证明了基于支架的疫苗的疫苗接种位置的灵活性，与引流LN距离无关。
The delivery location of traditional vaccines can impact immune responses and resulting efficacy. Cryogel-based cancer vaccines, which are typically injected near the inguinal lymph nodes (iLNs), recruit and activate dendritic cells (DC)in situ, induce DC homing to the iLNs, and have generated potent anti-tumor immunity against several murine cancer models. However, whether cryogel vaccination distance to a draining LN affects the kinetics of DC homing and downstream antigen-specific immunity is unknown, given the heightened importance of the scaffold vaccine site. We hypothesized that vaccination near the iLNs would lead to more rapid DC trafficking to the iLNs, thereby inducing faster and stronger immune responses. Here, mice were injected with cryogel vaccines against ovalbumin either adjacent or distal to the iLNs, and the resultant DC trafficking kinetics, T cell phenotypes, antigen-specific T cell and humoral responses, and prophylactic efficacy in an ovalbumin-expressing tumor model were assessed. Cryogel vaccines induced potent, long-lasting antigen-specific immune responses independent of distance to the iLNs, with no significant differences in DC trafficking kinetics, ovalbumin-specific T cell and antibody responses, or prophylactic efficacy. Moreover, DC trafficking and activation state were not impacted when cryogels were injected near a tumor. These results demonstrate a flexibility in vaccination location for scaffold-based vaccines, independent of draining LN distance.
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影响因子：
2.2
作者：
Harrell, Maria I.;Iritani, Brian M.;Ruddell, Alanna
通讯作者：
Ruddell, Alanna
影响因子：
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通讯作者：
von der Weid PY
影响因子：
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Najibi AJ;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
3.1
作者：
Ribeiro-Gomes, Flavia L.;Roma, Eric Henrique;Peters, Nathan C.
通讯作者：
Peters, Nathan C.