Protection against pneumonic plague following oral immunization with a non-replicating vaccine
Protection against pneumonic plague following oral immunization with a non-replicating vaccine
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DOI：
10.1016/j.vaccine.2010.06.020
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发表时间：
2010-08-16
期刊：
影响因子：
5.5
通讯作者：
Dow, Steven
中科院分区：
文献类型：
--
作者：
Jones, Abby;Bosio, Catharine;Dow, Steven
鼠疫耶尔森氏菌是一种危险的细菌病原体，吸入后可迅速诱发致命的肺鼠疫。因此，需要稳定、安全和易于施用的粘膜疫苗，其能够引发针对肺Y的有效保护。鼠疫感染阳离子脂质体-核酸复合物（CLDC）先前已被证明是用于肠胃外免疫的有效疫苗佐剂，但先前尚未评估用于口服免疫。因此，我们研究了口服CLDC佐剂疫苗引发针对致死性肺鼠疫的保护性免疫的能力。用10 μ g Y.评估鼠疫F1抗原与CLDC组合的免疫应答和对攻击的保护。我们发现，口服免疫引起高滴度的抗F1抗体，相当于那些产生的胃肠外免疫。重要的是，口服免疫的小鼠可以保护免受致命的肺攻击与有毒的Y。接种疫苗后18周内感染鼠疫。口服免疫后疫苗诱导的保护作用主要依赖于CD 4 + T细胞，部分来自CD 8 + T细胞。因此，CLDC佐剂疫苗代表了一种新型的口服给药的非复制型疫苗，能够产生有效的保护作用，以对抗强毒Y。鼠疫(C)2010年由Elsevier Ltd.出版
Yersinia pestis is a dangerous bacterial pathogen that when inhaled can rapidly induce fatal pneumonic plague. Thus, there is a need for stable, safe, and easily administered mucosal vaccines capable of eliciting effective protection against pulmonary Y. pestis infections. Cationic liposome-nucleic acid complexes (CLDC) have been shown previously to be effective vaccine adjuvants for parenteral immunization, but have not been previously evaluated for use in oral immunization. Therefore, we investigated the ability of an orally administered CLDC adjuvanted vaccine to elicit protective immunity against lethal pneumonic plague. C57BI/6 mice were vaccinated orally or subcutaneously using 10 mu g Y. pestis F1 antigen combined with CLDC and immune responses and protection from challenge was assessed. We found that oral immunization elicited high titers of anti-F1 antibodies, equivalent to those generated by parenteral immunization. Importantly, orally immunized mice were protected from lethal pulmonary challenge with virulent Y. pestis for up to 18 weeks following vaccination. Vaccine-induced protection following oral immunization was found to be dependent primarily on CD4+ T cells, with a partial contribution from CD8+ T cells. Thus, CLDC adjuvanted vaccines represent a new type of orally administered, non-replicating vaccine capable of generating effective protection against pulmonary infection with virulent Y. pestis. (C) 2010 Published by Elsevier Ltd.