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

增强对细菌载体 Stre 传递的抗原的免疫反应

• 批准号: 7492158
• 负责人: DENNIS E. HRUBY
• 金额: $ 28.05万
• 依托单位: SIGA TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7492158
• 关键词: Antibodies; Antigens; Clinical Trials; Control Animal; Heterophile Antigens; Human; Immune response; Immunization; Modeling; Mus; Phase; Recombinants; Saliva; Serum; Streptococcus gordonii; Subunit Vaccines; Surface; System; Technology; Vaccination; Vaccinia; Vaccinia virus; Viral; Viral Proteins; bacterial vector; commensal microbes; cytokine; immunogenicity; interest; neutralizing antibody; pathogen; response; vaccine delivery; vaccinia virus vector; vector

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.

描述（由申请人提供）：该提案的重点是开发一种安全、有效的亚单位疫苗递送系统。为了实现这一目标，我们将利用我们的细菌共生载体 (BCV) 技术。 BCV 使用革兰氏阳性共生细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 菌株在人类中是安全且耐受性良好的。与对照动物相比，用表达痘苗病毒（VV）蛋白的戈登沙门氏菌对小鼠进行粘膜免疫可诱导唾液和血清中痘苗病毒特异性抗体显着增加。此外，从免疫小鼠获得的血清含有针对痘苗病毒的中和抗体。然而，用 BCV:VV 构建体免疫小鼠仅引起针对致命痘苗攻击的部分保护。我们假设 BCV 系统共表达免疫调节分子将增强对编码抗原的体液或细胞反应，从而提供安全、有效且廉价的亚单位疫苗递送系统，适用于对抗许多病毒或细菌病原体。为了进一步开发BCV系统，提出了以下具体目标：1）通过与模型抗原共表达细胞因子来增强S.gordonii重组体的免疫原性。 2) 评估用戈登沙门氏菌双重组体对小鼠鼻内接种疫苗后对模型抗原的体液和细胞免疫反应。