Effect of homologous and heterologous prime-boost on the immune response to recombinant plague antigens
Effect of homologous and heterologous prime-boost on the immune response to recombinant plague antigens
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DOI：
10.1016/j.vaccine.2004.10.025
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发表时间：
2005-03-14
期刊：
影响因子：
5.5
通讯作者：
Clements, JD
中科院分区：
文献类型：
--
作者：
Glynn, A;Freytag, LC;Clements, JD
在已被确定为生物战或生物恐怖主义潜在病原体的病原体中，鼠疫耶尔森氏菌是主要令人担忧的问题之一，因为这种疾病的神经元型在人类中具有严重的严重性和潜在的传播性。目前还没有被批准的预防肺炎鼠疫的疫苗，但一种鼠疫来源的融合蛋白(F1-V)在小鼠研究中显示出作为保护性抗原的巨大前景。在本研究中，我们考察了不同的PRIME-BOOST方案，包括肠外给药、粘膜给药和经皮给药，以探索改变PRIME和BOOST的途径对重组F1-V促进长效、高滴度抗体产生能力的影响。这项研究报告的最重要的发现是：(1)鼻内免疫和皮下免疫对于诱导血清和细支气管肺泡抗F1-V IgGI反应都是有效的且基本相同，(2)对于诱导血清或细支气管肺泡抗F1-V IgGI反应，异种免疫与同种免疫一样有效或比同种免疫有效或更有效；(3)与经皮或皮下注射的动物相比，鼻内免疫和经任何途径增强的抗F1-V和抗-V总免疫应答最高。与之前发表的研究一样，初级免疫后一年仍有大量循环中的抗F1-V抗体水平。这些研究为新一代生物防御疫苗的开发提供了重要的见解。(C)2004爱思唯尔有限公司。保留所有权利。
Among the pathogens that have been identified as potential agents of biological warfare or bioterrorism, Yersinia pestis is one of the main concerns due to the severity and potential transmissibility of the pneurnonic form of the disease in humans. There are no approved vaccines for protection against pneumonic plague, but a Y pestis-derived fusion protein (F1 -V) has shown great promise as a protective antigen in murine studies. In the current study, we examine different prime-boost regimens, including parenteral, mucosal, and transcutaneous delivery, in order to explore the effect of changing the route of prime and boost on the ability of recombinant F1-V to promote the development of long-lasting, high-titer antibodies. The most significant findings of the study reported here are that (1) intranasal and subcutaneous immunizations are both effective and essentially equivalent for induction of serum and bronchioalveolar anti-F1-V IgGI responses when a single booster dose is administered by the same (homologous) route, (2) heterologous boosting can be as or more effective than homologous boosting for induction of either serum or bronchioalveolar anti-F1-V IgGI responses, and (3) anti-F1 and anti-V total IgG responses were highest in animals primed intranasally and boosted by any route when compared to animals primed transcutaneously or subcutaneously. As with previously published studies, there were still significant levels of circulating anti-F1-V antibodies I year post-primary immunization. These studies provide important insights into the development of new-generation biodefense vaccines. (c) 2004 Elsevier Ltd. All rights reserved.