Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model.
Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model.
复制标题
DOI：
10.1016/j.vaccine.2012.11.042
复制
发表时间：
2013-01-11
期刊：
影响因子：
5.5
通讯作者：
Rivas-Santiago B
中科院分区：
文献类型：
--
作者：
Cervantes-Villagrana AR;Hernández-Pando R;Biragyn A;Castañeda-Delgado J;Bodogai M;Martínez-Fierro M;Sada E;Trujillo V;Enciso-Moreno A;Rivas-Santiago B
据世界卫生组织（WHO）估计，每年约有800万新的活动性结核病（TB）病例。尽管其不规则的有效性（0-89%），卡介苗是全球唯一可用于预防结核病的疫苗;因此，设计新颖且更有效的疫苗接种策略是重要的。考虑到β-防御素-2（β-defensin-2）是一种通过TLR-4受体诱导树突状细胞成熟的抗菌肽，而ESAT-6和Ag 85 B都是分枝杆菌的免疫优势抗原，是有效的保护性免疫激活剂，因此我们将β-防御素-2基因分别与ESAT-6（pDE）和Ag 85 B（pDA）融合，构建了两种DNA疫苗。在确认有效的局部抗原表达后，在肌内（i. m.）接种Balb/c小鼠后，用DNA疫苗以初免-加强方案用BCG和单独用BCG接种小鼠组，2个月后用温和毒力参考菌株H37 Rv和高毒力临床分离株LAM 5186攻击。通过存活率、肺杆菌负荷和组织损伤（肺炎）的扩展来评价保护水平。用这两种DNA疫苗接种显示出与BCG相似的保护作用。在用高毒性结核分枝杆菌菌株攻击后，用BCG初免加强然后用两种DNA疫苗加强的动物显示出比仅用BCG接种的小鼠显著更高的存活率和更少的组织损伤。这些结果表明，BCG疫苗接种的改进，如初免-加强DNA疫苗，代表了一种更有效的结核病疫苗接种方案。
The World Health Organization (WHO) has estimated that there are about 8 million new cases annually of active Tuberculosis (TB). Despite its irregular effectiveness (0–89%), the Bacillus Calmette-Guérin) BCG is the only vaccine available worldwide for prevention of TB; thus, the design is important of novel and more efficient vaccination strategies. Considering that β-defensin-2 is an antimicrobial peptide that induces dendritic cell maturation through the TLR-4 receptor and that both ESAT-6 and Ag85B are immunodominant mycobacterial antigens and efficient activators of the protective immune response, we constructed two DNA vaccines by the fusion of the gene encoding β-defensin-2 and antigens ESAT6 (pDE) and 85B (pDA). After confirming efficient local antigen expression that induced high and stable Interferon gamma (IFN-γ) production in intramuscular (i.m.) vaccinated Balb/c mice, groups of mice were vaccinated with DNA vaccines in a prime-boost regimen with BCG and with BCG alone, and 2 months later were challenged with the mild virulence reference strain H37Rv and the highly virulent clinical isolate LAM 5186. The level of protection was evaluated by survival, lung bacilli burdens, and extension of tissue damage (pneumonia). Vaccination with both DNA vaccines showed similar protection to that of BCG. After the challenge with the highly virulent Mycobacterium tuberculosis strain, animals that were prime-boosted with BCG and then boosted with both DNA vaccines showed significant higher survival and less tissue damage than mice vaccinated only with BCG. These results suggest that improvement of BCG vaccination, such as the prime-boost DNA vaccine, represents a more efficient vaccination scheme against TB.
登录
查看更多内容
影响因子：
3.1
作者：
Armitige, LY;Jagannath, C;Norris, SJ
通讯作者：
Norris, SJ
影响因子：
15.9
作者：
Hinchey, Joseph;Lee, Sunhee;Porcelli, Steven A.
通讯作者：
Porcelli, Steven A.
影响因子：
5.5
作者：
Brun, Paola;Zumbo, Antonella;Manganelli, Riccardo
通讯作者：
Manganelli, Riccardo
影响因子：
46.9
作者：
Biragyn, A;Tani, K;Kwak, LW
通讯作者：
Kwak, LW
影响因子：
4.2
作者：
Berrêdo-Pinho M;Kalume DE;Correa PR;Gomes LH;Pereira MP;da Silva RF;Castello-Branco LR;Degrave WM;Mendonça-Lima L
通讯作者：
Mendonça-Lima L