The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.
The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.
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DOI：
10.1371/journal.pone.0039909
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dietrich J
中科院分区：
文献类型：
--
作者：
Billeskov R;Elvang TT;Andersen PL;Dietrich J
目前的结核病疫苗(BCG)未能在全球范围内控制结核病，而且保护效力仅限于10-15年。因此，一种能够有效增强卡介苗诱导的免疫反应并从而延长保护性免疫的疫苗将对全球结核病负担产生重大影响。在本研究中，我们证明了由分枝杆菌抗原Ag85B和TB10.4组成的融合蛋白HyVac4(H4)在佐剂IC31®或DDA/MPL中给予有效地增强和延长了BCG诱导的免疫，导致了对强毒结核分枝杆菌(M.tb)感染的更好的保护。增强的保护力与感染部位产生γ/α/IL-2或肿瘤坏死因子α/IL-2的特异性干扰素CD4T细胞的百分比增加有关。此外，这一疫苗策略没有影响ESAT-6作为疾病发展/疫苗效力的准确相关性的使用。事实上，CD4和CD8ESAT-6特异性T细胞都与细菌水平显着相关。H4-IC31®可有效增强卡介苗诱导的免疫应答，增强以干扰素γ/肿瘤坏死因子α/IL-2或肿瘤坏死因子α/IL 2为主的保护性抗结核分枝杆菌免疫应答。H4在CD4T细胞中诱导佐剂IC31®目前正在进行临床试验。
The current vaccine against tuberculosis (TB), BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10–15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. In the present study we show that the fusion protein HyVac4 (H4), consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb). Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.