Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination
Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination
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DOI：
10.1016/j.vaccine.2010.07.087
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发表时间：
2010-10-08
期刊：
影响因子：
5.5
通讯作者：
Marsh, Philip D.
中科院分区：
文献类型：
--
作者：
Clark, Simon O.;Kelly, Dominic L. F.;Marsh, Philip D.
需要一种改进的疫苗来更好地控制人类结核病（TB），因为目前唯一可用的TB疫苗，即经肠胃外递送的卡介苗（BCG），提供不同水平的功效。因此，表达额外抗原的重组菌株正在与胃肠外递送的替代途径一起开发。有强有力的证据表明，卡介苗莫罗（RdJ）是一种安全有效的疫苗，在人类时，通过口服途径。本研究比较了单次口服剂量的野生型BCG Moreau Rio de Janeiro（RdJ）或表达Ag 85 B-ESAT 6融合蛋白的重组RdJ菌株（配制有或不配制有脂质以增强口服递送）与皮下BCG Danish 1331和盐水对照组在豚鼠肺结核气溶胶感染模型中的功效。保护作用以攻毒后30周的存活率以及肺和脾中细菌负荷和组织病理学的降低来衡量。结果显示，单次口服剂量的BCG Moreau（RdJ）或重组BCG Moreau（RdJ）-Ag 85 B-ESAT 6（与或不与脂质一起配制）在30周的攻击后存活研究中提供与皮下递送的BCG Danish等同的保护。与皮下递送的BCG Danish相比，口服递送的疫苗在肺（四种制剂中的三种）和脾（所有四种制剂）中的病理学评分降低。与皮下递送的BCG Danish相比，脂质中的口服野生型BCG Moreau（RdJ）和未配制的口服野生型BCG Moreau（RdJ）疫苗也分别在肺和脾中产生统计学上更低的细菌负荷。这项研究提供了进一步的证据，表明脂质制剂不会损害疫苗的有效性，并可能提高预期用于卫生基础设施较差国家的口服疫苗的递送和稳定性。口服给药还避免了针头（和相关的交叉感染风险）和免疫接种，而不需要经过专门培训的医疗专业人员。皇冠版权所有（C）2010由爱思唯尔有限公司出版。保留所有权利。
There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained medical professional staff. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.