H INFLUENZAE VACCINE BASED ON RECOMBINANT BCG

卡介苗和分枝杆菌减毒株 以活的形式用来为人类接种疫苗的牛王 结核病为发展提供了许多独特的优势 多价疫苗载体。最近，通用的向量 重组卡介苗(RBCG)中异源蛋白的表达 发展起来的。进一步提高异种抗原的免疫原性 在rBCG中，我们构建了新的rBCG表达载体 编码分枝杆菌脂蛋白的序列对体内酰化的影响 并将重组抗原输出到rBCG表面。其他人则有 先前的研究表明，酰化可以增强体液和细胞 对各种蛋白质的反应。重组人的初步结果 伯氏疏螺旋体脂蛋白抗原OspA显示，融合- 脂蛋白载体可以实现所需的生化修饰和 增强该蛋白质的免疫应答。为了进一步测试该系统 我们建议构建表达高度保守的卡介苗重组体 流感嗜血杆菌P6脂蛋白，一个已证实的靶标 保护性抗体。这些拟议的研究将提供有用的见解 将rBCG作为活疫苗载体的潜力，用于融合- 脂蛋白方法，并将产生一种新的候选疫苗 这两种疾病都是由b型和无包膜流感嗜血杆菌引起的。

BCG (Bacille Calmette-Guerin), and attenuated strain of Mycobacterium bovis that is used in viable form to vaccinate humans against tuberculosis, offers a number of unique advantages for development as a multivalent vaccine vehicle. Recently, versatile vectors for the expression of heterologous proteins in recombinant BCG (rBCG) have been developed. To further improve the immunogenicity of heterologous antigens in rBCG we have constructed new rBCG expression vectors employing sequences encoding mycobacterial lipoproteins to effect in vivo acylation and export of recombinant antigens to the surface of rBCG. Others had previously shown that acylation can enhance the humoral and cellular responses to various proteins. Preliminary results with the recombinant lipoprotein antigen OspA of Borrelia burgdorferi show that the fusion- lipoprotein vectors can effect the desired biochemical modifications and immune response enhancement for this protein. To further test this system we propose to construct BCG recombinants expressing the highly conserved P6 lipoprotein of Haemophilus influenzae, a demonstrated target for protective antibodies. These proposed studies will provide useful insight into the potential for rBCG as a live vaccine vehicle, for the fusion- lipoprotein approach, and will also yield a new candidate vaccine for disease caused by both type b ad unencapsulated H. influenzae.