ISS-linked NP vaccine to control pandemic flu outbreak

与 ISS 相关的 NP 疫苗可控制大流行性流感爆发

• 批准号: 6853609
• 负责人: Gary A Van Nest
• 金额: $ 53.48万
• 依托单位: DYNAVAX TECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-11 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853609
• 关键词: baboons; cooperative study; cytotoxic T lymphocyte; genetic strain; helper T lymphocyte; immunoconjugates; influenza vaccines; influenzavirus A; laboratory mouse; nonhuman therapy evaluation; nucleoproteins; oligonucleotides; vaccine development; virus antigen

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and evaluate a novel influenza vaccine that incorporates conserved internal components of influenza virus such as the nucleoprotein (NP) with a potential to induce protective immunity against divergent and potentially pandemic influenza strains. The hypothesis of this proposal is that the nucleoprotein (NP) of influenza virus linked to an immunostimulatory oligonucleotide (ISS) will induce strong Th1 and CTL responses that will cross-react with widely divergent influenza A strains due to the conserved nature of the nucleoprotein molecule. The immune response induced by the NP-ISS linked material may additionally provide cross-help to enhance the response to other viral antigens such as HA, when co-administered in a vaccine, or when subsequently encountered in association with NP during viral infection. The Specific Aims of the program are: 1. Produce a nucleoprotein immunostimulatory oligonucleotide conjugate (NP-ISS) and demonstrate potent induction of Th1 and CTL responses by the NP-ISS vaccine in naive and previously infected mice. 2. Evaluate the protective immunity provided by the NP-ISS vaccine, or NP-ISS mixed with monovalent inactivated whole virus vaccine against homologous and divergent influenza strains in mice. 3. Test the immunogenicity of NP-ISS, and NP-ISS combined with standard split vaccine in primates compared to standard split vaccine alone. 4. Perform GMP scale-up manufacture and IND-enabling toxicology with NP-ISS. Assuming success in each Specific Aim, this program is intended to produce an IND-ready product that could rapidly move into clinical testing.

描述（由申请人提供）：本申请的目标是开发和评估一种新型流感疫苗，该疫苗包含流感病毒的保守内部成分，如核蛋白（NP），具有诱导针对不同和潜在大流行性流感毒株的保护性免疫的潜力。这一提议的假设是，由于核蛋白分子的保守性，与免疫刺激寡核苷酸（ISS）连接的流感病毒核蛋白（NP）将诱导强烈的Th1和CTL反应，这些反应将与广泛分化的甲型流感毒株交叉反应。NP- iss连接材料诱导的免疫应答，当与疫苗共同使用时，或在病毒感染期间与NP相关时，可能还提供交叉帮助，以增强对其他病毒抗原（如HA）的应答。该计划的具体目标是：