H INFLUENZAE VACCINE BASED ON RECOMBINANT BCG

卡介苗（Bacille Calmette-Guerin）和分枝杆菌减毒株 以活的形式用于给人类接种抗 结核病，为发展提供了一些独特的优势， 多价疫苗载体。最近，用于 在重组BCG（rBCG）中表达异源蛋白质已经被 开发进一步提高异源抗原的免疫原性 在rBCG中，我们构建了新的rBCG表达载体， 编码分枝杆菌脂蛋白以实现体内酰化的序列 并将重组抗原输出到rBCG的表面。其他人 先前表明，酰化可以增强体液和细胞 对各种蛋白质的反应。 重组体的初步结果 伯氏疏螺旋体的脂蛋白抗原OspA显示融合- 脂蛋白载体可以实现所需的生化修饰 免疫反应增强这种蛋白质。为了进一步测试这个系统 我们建议构建表达高度保守的 流感嗜血杆菌的P6脂蛋白， 保护性抗体这些拟议的研究将提供有益的见解 rBCG作为活疫苗载体的潜力， 脂蛋白的方法，也将产生一个新的候选疫苗， 由B型和未包囊的H.流感。

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.