Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations.
Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations.
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DOI：
10.1016/j.tube.2016.09.004
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Dennis M
中科院分区：
文献类型：
--
作者：
Sharpe S;White A;Sarfas C;Sibley L;Gleeson F;McIntyre A;Basaraba R;Clark S;Hall G;Rayner E;Williams A;Marsh PD;Dennis M
皮内（ID）BCG注射在人类和实验模型中对结核病提供了不完全的保护。替代BCG疫苗接种策略可以提高模型物种（包括恒河猴）的保护作用。本研究比较了BCG通过ID和静脉（IV）注射或作为肠道粘膜加强（ID + IT）给药对抗结核分枝杆菌Erdman菌株气溶胶攻击的免疫原性和有效性。相对于未接种疫苗的动物，每种BCG疫苗接种策略均显著降低了疾病病理学，并提高了存活率。然而，IV诱导的保护作用超过了所有其他途径，这为使用抗原特异性IFN-γ ELISpot和多色流式细胞术检测探索保护性免疫机制提供了机会。IFN-γ斑点形成单位和多功能CD 4 T细胞频率在每个疫苗接种方案后显著增加，并且在IV免疫后最大。疫苗诱导的产生IFN-γ和TNF-α的多功能CD 4 T细胞与随后的结核分枝杆菌攻毒后疾病病理学减轻相关;然而，结核分枝杆菌感染后该群体的高频率与病理学增加相关。产生细胞因子的T细胞主要占据CD 4过渡效应记忆表型，暗示该群体是分枝杆菌应答的中心，可能有助于在IV接种动物中观察到的严格控制。本研究证明了静脉接种卡介苗在恒河猴中的保护效果，为询问免疫机制和保护的潜在相关性提供了有价值的工具。
Intradermal (ID) BCG injection provides incomplete protection against TB in humans and experimental models. Alternative BCG vaccination strategies may improve protection in model species, including rhesus macaques. This study compares the immunogenicity and efficacy of BCG administered by ID and intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT), against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease pathology was significantly reduced, and survival improved, by each BCG vaccination strategy, relative to unvaccinated animals. However, IV induced protection surpassed that achieved by all other routes, providing an opportunity to explore protective immunological mechanisms using antigen-specific IFN-γ ELISpot and polychromatic flow cytometry assays. IFN-γ spot forming units and multifunctional CD4 T-cell frequencies increased significantly following each vaccination regimen and were greatest following IV immunisation. Vaccine-induced multifunctional CD4 T-cells producing IFN-γ and TNF-α were associated with reduced disease pathology following subsequent M.tb challenge; however, high frequencies of this population following M.tb infection correlated with increased pathology. Cytokine producing T-cells primarily occupied the CD4 transitional effector memory phenotype, implicating this population as central to the mycobacterial response, potentially contributing to the stringent control observed in IV vaccinated animals. This study demonstrates the protective efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for the interrogation of immunological mechanisms and potential correlates of protection.
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影响因子：
--
作者：
Aguilo, Nacho;Toledo, Ana Maria;Martin, Carlos
通讯作者：
Martin, Carlos
DOI：
10.4049/jimmunol.1101122
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
通讯作者：
Hanekom WA
DOI：
10.1017/s0022172400041851
发表时间：
1969-01-01
期刊：
JOURNAL OF HYGIENE-CAMBRIDGE
影响因子：
--
作者：
DRUETT, HA
通讯作者：
DRUETT, HA
DOI：
10.1164/rccm.201003-0334oc
发表时间：
2010-10-15
影响因子：
24.7
作者：
Kagina, Benjamin M. N.;Abel, Brian;Hanekom, Willem A.
通讯作者：
Hanekom, Willem A.
影响因子：
3.1
作者：
Chackerian, AA;Perera, TV;Behar, SM
通讯作者：
Behar, SM