Enhancing the immune response to antigens delivered by the bacterial vector, Stre

描述（由申请方提供）：本提案的重点是开发一种安全、有效的亚单位疫苗给药系统。为了实现这一目标，我们将利用我们的细菌载体（BCV）技术。BCV使用革兰氏阳性球菌戈登链球菌在其外表面表达感兴趣的异源抗原。I期人体临床试验表明，这种S。Gordonii菌株在人体中是安全的且耐受性良好。用S.与对照动物相比，表达牛痘病毒（VV）蛋白的gordonii在唾液和血清中诱导显著增加的牛痘病毒特异性抗体。此外，从免疫小鼠获得的血清含有针对牛痘病毒的中和抗体。然而，用BCV：VV构建体免疫小鼠仅引起对致死性牛痘攻击的部分保护。我们假设，免疫调节分子的共表达的BCV系统将增强体液或细胞对编码的抗原的反应，从而提供了一个安全，有效，廉价的亚单位疫苗输送系统，适用于对许多病毒或细菌病原体。为了进一步发展该系统，提出了以下具体目标：1）增强S.通过共表达细胞因子与模型抗原来构建Gordonii重组体。2)目的评价小鼠鼻内接种沙门氏菌后对模型抗原的体液和细胞免疫应答。gordonii双重组体。

DESCRIPTION (provided by applicant): The focus of this proposal is to develop a safe, effective subunit vaccine delivery system. To accomplish this, we will utilize our bacterial commensal vector (BCV) technology. BCV uses the Gram-positive commensal bacteria, Streptococcus gordonii, to express heterologous antigens of interest on its external surface. Phase I human clinical trials indicate that this S. gordonii strain is safe and well-tolerated in humans. Mucosal immunization of mice with S. gordonii expressing vaccinia virus (VV) proteins induced significantly increased vaccinia virus specific antibodies in saliva and serum compared to control animals. Furthermore, serum obtained from immunized mice contained neutralizing antibodies against vaccinia virus. However, immunization of mice with the BCV:VV constructs elicited only partial protection against lethal vaccinia challenge. We hypothesize that co-expression of immunomodulatory molecules by the BCV system will enhance humoral or cellular responses to the encoded antigens, thus providing a safe, effective, and inexpensive subunit vaccine delivery system suitable for use against many viral or bacterial pathogens. To further develop the BCV system the following specific aims are proposed: 1) To enhance the immunogenicity of S. gordonii recombinants by co-expressing cytokines with a model antigen. 2) To evaluate humoral and cellular immune responses to the model antigen after intranasal vaccination of mice with the S. gordonii double recombinants.