Medical Research Unit-Zacatecas, Mexican Institute of Social Security IMSS, Zacatecas, Mexico.
Vaccine. 2013 Jan 11;31(4):676-84. doi: 10.1016/j.vaccine.2012.11.042. Epub 2012 Nov 26.
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.
世界卫生组织（WHO）估计每年约有 800 万例活动性肺结核（TB）新发病例。尽管卡介苗（BCG）的效果并不稳定（0-89%），但它仍是全球唯一可用于预防结核病的疫苗；因此，设计新型、更有效的疫苗接种策略非常重要。考虑到β-防御素-2 是一种抗菌肽，可通过 TLR-4 受体诱导树突状细胞成熟，而 ESAT-6 和 Ag85B 均为免疫优势的分枝杆菌抗原，能有效激活保护性免疫反应，我们构建了两种 DNA 疫苗，即将编码β-防御素-2 的基因与抗原 ESAT6（pDE）和 85B（pDA）融合。在确认在肌肉内（i.m.）接种的 Balb/c 小鼠中能有效局部表达抗原，并诱导高且稳定的干扰素γ（IFN-γ）产生后，用 DNA 疫苗对几组小鼠进行了 BCG 初免-加强免疫接种，并与单独使用 BCG 进行了比较，2 个月后用低毒力参考株 H37Rv 和高毒力临床分离株 LAM 5186 进行攻毒。通过生存、肺内细菌负荷和组织损伤（肺炎）的扩展来评估保护水平。两种 DNA 疫苗的接种均显示出与 BCG 相似的保护作用。在高毒力结核分枝杆菌菌株的攻毒后，用 BCG 初免-加强免疫，然后用两种 DNA 疫苗加强免疫的动物的生存率和组织损伤明显高于仅用 BCG 接种的小鼠。这些结果表明，改善 BCG 接种，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。
