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安全，有效的亚基疫苗输送系统。为此，我们将利用我们的细菌共生载体（BCV）技术。 BCV使用革兰氏阳性的共生细菌链球菌Gordonii在其外表面上表达有兴趣的异源抗原。 I期人类临床试验表明，这种Gordonii菌菌株在人类中是安全且耐受性良好的。与对照动物相比，用表达牛ac病毒（VV）蛋白的小鼠粘膜免疫可显着增加唾液和血清中的牛ac病毒特异性抗体。此外，从免疫小鼠获得的血清中含有对离甲酸病毒的中和抗体。然而，用BCV：VV构建的小鼠免疫仅引起了针对致命疫苗挑战的部分保护。我们假设通过BCV系统对免疫调节分子的共表达将增强对编码抗原的体液或细胞反应，从而提供适合用于许多病毒或细菌病原体的安全，有效且廉价的亚基疫苗递送系统。为了进一步开发BCV系统，提出了以下特定目的：1）通过与模型抗原共表达细胞因子来增强戈多尼重组剂的免疫原性。 2）评估用S. gordonii双重重组剂对小鼠鼻内疫苗接种后对模型抗原的体液和细胞免疫反应。