Novel nanoparticulate adjuvants to enhance HIV-1 Env specific mucosal antibody responses

新型纳米颗粒佐剂增强 HIV-1 Env 特异性粘膜抗体反应

基本信息

  • 批准号:
    10413110
  • 负责人:
  • 金额:
    $ 88.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-03 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Abstract One of the key obstacles to developing an effective HIV-1 vaccine is identifying adjuvants and immunogens that induce persistent HIV-1 envelope (Env) antigen specific antibody responses of high magnitude. Alum has been the choice of adjuvant for use in humans for almost a century now and also used in most HIV-1 vaccine clinical trials. However, Alum fails to induce persistent HIV-1 Env specific antibody responses of the appropriate quality (neutralizing activity or effector functions). Nanoparticulate adjuvants are known to enhance immune responses by rapidly draining and targeting key immune cells in lymph nodes. Our recently completed studies evaluating a novel TLR-7/8 ligand (3M-052) from 3M Pharmaceuticals by itself or in combination with a TLR-4 agonist GLA formulated in biodegradable synthetic polymer nanoparticles in rhesus macaques has for the first time successfully induced HIV-1 Env specific long-lived plasma cells (LLPCs) in the bone marrow. Robust and persistent antibody responses with binding, neutralizing and ADCC activity were also observed at high magnitude in addition to high frequencies of germinal center B cells and follicular T helper cells in draining lymph nodes. However, our polymer nanoparticles have faced challenges with manufacturability for use in humans. Hence, building on our proof of concept studies, in collaboration with the Infectious Disease Research Institute (IDRI) and 3M Pharmaceuticals, we now propose to a) evaluate a NanoAlum, novel clinically relevant Alum based nanoparticulate adjuvant with HIV-1 Env immunogens in combination with the 3M-052 molecule, b) establish new methodology that uses novel serum proteomics and BCR sequencing to rigorously investigate vaccine induced responses by defining key subsets of LLPCs in RMs and finally c) evaluate vaccine based protective efficacy upon virus challenge when combining sub-cutaneous vaccinations with such new adjuvants with intranasal vaccinations (IN) to improve mucosal immunity at genital mucosa.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Sudhir Pai Kasturi其他文献

Cross-presentation: avoiding trafficking chaos?
交叉呈递:避免交通混乱?
  • DOI:
    10.1038/ni0508-461
  • 发表时间:
    2008-05-01
  • 期刊:
  • 影响因子:
    27.600
  • 作者:
    Sudhir Pai Kasturi;Bali Pulendran
  • 通讯作者:
    Bali Pulendran

Sudhir Pai Kasturi的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Sudhir Pai Kasturi', 18)}}的其他基金

Novel nanoparticulate adjuvants to enhance HIV-1 Env specific mucosal antibody responses
新型纳米颗粒佐剂增强 HIV-1 Env 特异性粘膜抗体反应
  • 批准号:
    10657401
  • 财政年份:
    2019
  • 资助金额:
    $ 88.31万
  • 项目类别:
Novel nanoparticulate adjuvants to enhance HIV-1 Env specific mucosal antibody responses
新型纳米颗粒佐剂增强 HIV-1 Env 特异性粘膜抗体反应
  • 批准号:
    10194358
  • 财政年份:
    2019
  • 资助金额:
    $ 88.31万
  • 项目类别:
Modulating durability of HIV-1 env specific humoral immunity with a novel TLR7/8 targeted formulation
用新型 TLR7/8 靶向制剂调节 HIV-1 包膜特异性体液免疫的持久性
  • 批准号:
    9205089
  • 财政年份:
    2016
  • 资助金额:
    $ 88.31万
  • 项目类别:

相似海外基金

AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
  • 批准号:
    10933287
  • 财政年份:
    2023
  • 资助金额:
    $ 88.31万
  • 项目类别:
Augmenting the Quality and Duration of the Immune Response with a Novel TLR2 Agonist-Aluminum Combination Adjuvant
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
  • 批准号:
    10499193
  • 财政年份:
    2021
  • 资助金额:
    $ 88.31万
  • 项目类别:
A Novel TLR5 Agonist-Based Adjuvant for Poliovirus Vaccine
一种基于 TLR5 激动剂的新型脊髓灰质炎病毒疫苗佐剂
  • 批准号:
    9305008
  • 财政年份:
    2016
  • 资助金额:
    $ 88.31万
  • 项目类别:
Angiogenesis antagonist plus CD40-TLR agonist adjuvant combination vaccine
血管生成拮抗剂加CD40-TLR激动剂佐剂组合疫苗
  • 批准号:
    8054408
  • 财政年份:
    2010
  • 资助金额:
    $ 88.31万
  • 项目类别:
Angiogenesis antagonist plus CD40-TLR agonist adjuvant combination vaccine
血管生成拮抗剂加CD40-TLR激动剂佐剂组合疫苗
  • 批准号:
    7909550
  • 财政年份:
    2010
  • 资助金额:
    $ 88.31万
  • 项目类别:
Malaria vaccines modified with TLR agonist adjuvant
TLR 激动剂佐剂修饰的疟疾疫苗
  • 批准号:
    8126073
  • 财政年份:
    2010
  • 资助金额:
    $ 88.31万
  • 项目类别:
Malaria vaccines modified with TLR agonist adjuvant
TLR 激动剂佐剂修饰的疟疾疫苗
  • 批准号:
    7899536
  • 财政年份:
    2009
  • 资助金额:
    $ 88.31万
  • 项目类别:
C5a Agonist as a Vaccine Adjuvant for the Aged
C5a 激动剂作为老年人的疫苗佐剂
  • 批准号:
    7362543
  • 财政年份:
    2007
  • 资助金额:
    $ 88.31万
  • 项目类别:
C5a Agonist as a Vaccine Adjuvant for the Aged
C5a 激动剂作为老年人的疫苗佐剂
  • 批准号:
    7502193
  • 财政年份:
    2007
  • 资助金额:
    $ 88.31万
  • 项目类别:
C5a Agonist as a Vaccine Adjuvant for the Aged
C5a 激动剂作为老年人的疫苗佐剂
  • 批准号:
    7911043
  • 财政年份:
    2007
  • 资助金额:
    $ 88.31万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了