Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses

脂质纳米颗粒作为新型佐剂诱导有效的滤泡辅助性 T 细胞和体液免疫反应

基本信息

  • 批准号:
    10461926
  • 负责人:
  • 金额:
    $ 62.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level of protection against a variety of dangerous illnesses. However, there are multiple pathogens for which no effective vaccines are available. Protective immunity against many pathogens can be achieved through long- lived and high-affinity antibody responses, which are driven by T follicular helper (Tfh) cells. Tfh cells are required for the formation and maintenance of germinal centers (GC), where B cell affinity maturation, class switch, and development of long-lived plasma and memory B cells occur. Thus, the magnitude or quality of antibody responses induced by a vaccine is shaped by its ability to induce Tfh cells. The identification of vaccine platforms or adjuvants that induce potent Tfh cell responses and broadly protective and durable antibody responses is a critical need in vaccinology. We have identified a potent vaccine adjuvant, lipid nanoparticles (LNPs), which induce strong Tfh cell differentiation and durable antibody responses after a single immunization when combined with protein subunits, inactivated virus or antigen-encoding mRNA. Importantly, our preliminary studies demonstrated the superiority of LNP's adjuvant activity over the FDA-approved vaccine adjuvant, MF59, in comparative studies. This proposal will aim to extend our preliminary findings, examine LNP's adjuvanticity in non-human primate immunization studies and investigate the mechanisms of action of LNPs. In 3 specific aims we will: 1.) Determine LNP's adjuvanticity in multiple vaccine platforms in mice. 2.) Assess the potency of LNP-adjuvanted Zika vaccines in non-human primates. 3.) Uncover LNP-induced immune mechanisms that regulate the biology of Tfh cells. This proposal aims to demonstrate that LNPs can be used as adjuvants in various conventional (inactivated pathogen and protein subunits) and unconventional (mRNA, DNA) vaccine types to induce strong Tfh cell and durable neutralizing antibody responses. This finding could have a significant impact on vaccine development as no licensed vaccines or adjuvants have been shown to potently activate Tfh cells that are critical for durable protective antibody responses against many pathogens. We believe that the data generated in this proposal will be capable of moving this vaccine adjuvant towards clinical trials.
摘要

项目成果

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Norbert Pardi其他文献

Norbert Pardi的其他文献

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{{ truncateString('Norbert Pardi', 18)}}的其他基金

Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses
脂质纳米颗粒作为新型佐剂诱导有效的滤泡辅助性 T 细胞和体液免疫反应
  • 批准号:
    10028088
  • 财政年份:
    2020
  • 资助金额:
    $ 62.64万
  • 项目类别:
Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses
脂质纳米颗粒作为新型佐剂诱导有效的滤泡辅助性 T 细胞和体液免疫反应
  • 批准号:
    10251324
  • 财政年份:
    2020
  • 资助金额:
    $ 62.64万
  • 项目类别:
Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses
脂质纳米颗粒作为新型佐剂诱导有效的滤泡辅助性 T 细胞和体液免疫反应
  • 批准号:
    10685476
  • 财政年份:
    2020
  • 资助金额:
    $ 62.64万
  • 项目类别:
Development of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNA
使用核苷修饰信使 RNA 开发通用流感病毒疫苗
  • 批准号:
    10170233
  • 财政年份:
    2019
  • 资助金额:
    $ 62.64万
  • 项目类别:
Development of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNA
使用核苷修饰信使 RNA 开发通用流感病毒疫苗
  • 批准号:
    10404632
  • 财政年份:
    2019
  • 资助金额:
    $ 62.64万
  • 项目类别:
Development of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNA
使用核苷修饰信使 RNA 开发通用流感病毒疫苗
  • 批准号:
    10624973
  • 财政年份:
    2019
  • 资助金额:
    $ 62.64万
  • 项目类别:

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