Vaccination with self-launching RhCMV/SIV DNA vaccine vectors

使用自启动 RhCMV/SIV DNA 疫苗载体进行疫苗接种

基本信息

项目摘要

PROJECT SUMMARY/ABSRACT A prophylactic HIV vaccine would be of tremendous benefit for global health by helping to reduce the number of infected people. Similarly, new vaccine approaches are needed with the potential to reduce incidence of tuberculosis and malaria. RhCMV-vectored SIV vaccines have demonstrated tremendous potential for eliciting immune responses that can control SIV infection, but the unstable CMV genome and the relatively large proportion of non-infectious virions in vaccine stocks present major practical challenges, which have already delayed tests of CMV-vectored vaccines in human patients. Additionally, the need for a cold chain that is likely infeasible in some HIV-endemic areas is problematic. Here we describe and propose to test a vaccine platform based on delivery of the CMV- based vaccine vector genome in nucleic-acid form. We have shown that the delivered genomes are capable of initiating self-sustaining replication in vivo, and that this vector replication engenders immune responses that appear at least equal if not superior to those stimulated by (conventional) vaccination with encapsidated vaccine-vector particles. Successful completion of this R21 project will thus accelerate CMV-based vaccine development for HIV and potentially other diseases as well. Indeed, we believe that an advance such as this is required before CMV-vectored vaccines can have the positive impact on human health that is so hoped for by the field. The goal of this work is to provide a practical, cost-effective platform for cytomegalovirus-based vaccine delivery in vivo. Our hypothesis is that RhCMVdIL10-SIVgag and -SIVenv vaccines delivered as replication-competent, self-excising BAC DNA can elicit immune responses that have the unique character associated with RhCMV-vectored vaccination and that are protective against SIV. This hypothesis will be addressed in two specific aims using the rhesus macaque non-human primate model. Aim 1 will determine the optimal in vivo delivery method for replication and dissemination of, as well as host immune responses to, a novel, self-launching RhCMVdIL10-SIV vaccine. Three different methods of in vivo BAC DNA delivery will be tested for immunogenicity. Cellular and humoral immune responses, including the development of Mamu-E-restricted responses, will be assessed in addition to replication and dissemination of the vector. Aim 2 will test if RhCMVdIL10-SIVgag and -SIVenv vaccines are protective against SIV disease when delivered as self-launching BACs. We will determine the extent of protection achieved against low-dose, pathogenic SIV challenge following vaccination of macaques using the optimal delivery method identified in Aim 1. The novel vaccine vectors that are described in this proposal will solve many of the hurdles that are limiting the development of current CMV-based viral vectors and have broad applicability for other diseases that impact human health.
项目总结/ ABSRACT

项目成果

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DENNIS J. HARTIGAN-O'CONNOR其他文献

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{{ truncateString('DENNIS J. HARTIGAN-O'CONNOR', 18)}}的其他基金

Genetic adjuvants to elicit neutralizing antibodies against HIV
基因佐剂可引发抗艾滋病毒中和抗体
  • 批准号:
    10491642
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Nonhuman Primate Testing Center for Evaluation of Somatic Cell Genome Editing Tools: Antibodies Supplement
非人类灵长类动物体细胞基因组编辑工具评估测试中心:抗体补充​​剂
  • 批准号:
    10827650
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Data Management and Analysis Core
数据管理与分析核心
  • 批准号:
    10731712
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Project 2
项目2
  • 批准号:
    10731714
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Multi-omic understanding of the transformed host T-cell response to HIV following therapeutic vaccination
治疗性疫苗接种后转化宿主 T 细胞对 HIV 反应的多组学理解
  • 批准号:
    10731710
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Project 1
项目1
  • 批准号:
    10731713
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10731711
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
Center for Somatic Cell Genome Editing in Nonhuman Primates
非人类灵长类体细胞基因组编辑中心
  • 批准号:
    10773947
  • 财政年份:
    2023
  • 资助金额:
    $ 23.34万
  • 项目类别:
SCGE Administrative Supplement
SCGE行政补充
  • 批准号:
    10651526
  • 财政年份:
    2022
  • 资助金额:
    $ 23.34万
  • 项目类别:
CCR5 immunotoxins as components of HIV cure regimens
CCR5 免疫毒素作为 HIV 治疗方案的组成部分
  • 批准号:
    10664839
  • 财政年份:
    2022
  • 资助金额:
    $ 23.34万
  • 项目类别:

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