Induction of humoral and enhanced cellular immune responses by novel core-shell nanosphere- and microsphere-based vaccine formulations following systemic and mucosal administration
Induction of humoral and enhanced cellular immune responses by novel core-shell nanosphere- and microsphere-based vaccine formulations following systemic and mucosal administration
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DOI：
10.1016/j.vaccine.2009.03.047
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发表时间：
2009-06-02
期刊：
影响因子：
5.5
通讯作者：
Ensoli, Barbara
中科院分区：
文献类型：
--
作者：
Caputo, Antonella;Castaldello, Arianna;Ensoli, Barbara
以前描述过无阴离子表面活性剂的聚合物核壳纳米球和微球，其内核由聚甲基丙烯酸甲酯（PMMA）组成，外壳由水溶共聚物（Eudragit L100-55）组成。外壳与核心紧密相连，并具有羧基，能够通过静电相互作用吸附大量的天然碱性蛋白（抗原负载能力高达20%，w/w），同时保持其活性。在目前的研究中，我们在小鼠中评估了由这些纳米和微球以及HIV-1 Tat蛋白组成的新疫苗配方的安全性和免疫原性。通过不同的途径接种疫苗，包括肌肉注射、皮下注射或鼻内注射，并将结果与单独接种Tat或与明矾佐剂一起接种Tat进行比较。数据表明，纳米和微球/Tat配方是安全的，并在小鼠全身和/或粘膜免疫后诱导强大和持久的细胞和体液反应。这些递送系统可能在针对HIV-1的新型Tat蛋白疫苗中具有巨大的潜力，并有望用于其他蛋白疫苗。2009爱思唯尔有限公司版权所有。
Anionic surfactant-free polymeric core-shell nanospheres and microspheres were previously described with an inner core constituted by poly(methylmethacrylate) (PMMA) and a highly hydrophilic outer shell composed of a hydiosoluble co-polymer (Eudragit L100-55). The outer shell is tightly linked to the core and bears carboxylic groups capable of adsorbing high amounts (antigen loading ability of up to 20%, w/w) of native basic proteins, mainly by electrostatic interactions, while preserving their activity. In the present study we have evaluated in mice the safety and immunogenicity of new vaccine formulations composed of these nano- and microspheres and the HIV-1 Tat protein. Vaccines were administered by different routes, including intramuscular, subcutaneous or intranasal and the results were compared to immunization with Tat alone or with Tat delivered with the alum adjuvant. The data demonstrate that the nano- and microspheres/Tat formulations are safe and induce robust and long-lasting cellular and humoral responses in mice after systemic and/or mucosal immunization. These delivery systems may have great potential for novel Tat protein-based vaccines against HIV-1 and hold promise for other protein-based vaccines. (C) 2009 Elsevier Ltd. All rights reserved.