In vitro bioreactor production of a genetically modified late liver stage-arresting replication competent Plasmodium falciparum sporozoite vaccine

体外生物反应器生产具有复制能力的转基因晚期肝阶段恶性疟原虫子孢子疫苗

基本信息

  • 批准号:
    10634703
  • 负责人:
  • 金额:
    $ 30万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-03 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT In 2020 malaria caused 241M clinical episodes and 627,000 deaths, a significant increase from 2019. There were more deaths in Africa from malaria than from COVID-19. There is an urgent unmet medical need for a malaria vaccine that prevents infection and disease in individuals and can be deployed in mass vaccination programs for malaria elimination. Based on results of a pilot implementation program in >500,000 infants, RTS,S/AS01 was recommended in late 2021 by WHO for immunization of 5-month-olds with 4 immunizations administered over 21 months. RTS,S significantly reduced hospital admissions for malaria by 21% and severe malaria by 30%. It did not significantly reduce cerebral malaria, severe malaria anemia, or overall mortality, or prevent Plasmodium falciparum (Pf) infection. Of vaccines under development, only Sanaria’s PfSPZ vaccines have the efficacy against Pf infection to be considered for prevention of Pf infection in individuals or for geographically focused Pf malaria elimination campaigns. Sanaria’s 1st generation vaccine, PfSPZ Vaccine, is comprised of radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), which arrest early in the liver stage. Phase 3 clinical trials will begin in mid 2022, and marketing authorizations in Europe (EMA) and the US (FDA) are planned for 2023/2024. Sanaria’s 2nd generation vaccine is PfSPZ-CVac (Chemoprophylaxis Vaccine). In PfSPZ-CVac, the parasites replicate in the liver, biologically amplifying the immunogen load by up to 50,000-fold and then are killed by an anti-malarial drug. PfSPZ-CVac co-administered with chloroquine (CQ), gave 100% vaccine efficacy (VE) against heterologous controlled human malaria infection (CHMI) 12 weeks after vaccination using 22% the dose of PfSPZ needed to achieve 80% VE against heterologous CHMI with PfSPZ Vaccine. PfSPZ-CVac (CQ) is more protective than PfSPZ Vaccine at ~1/5 the dose. However, transient symptoms of malaria can occur after 1st dose of PfSPZ, and if CQ is not administered appropriately, parasite multiplication in the blood could cause severe malaria. To retain the enhanced potency of PfSPZ- CVac and eliminate its drawbacks, we genetically altered Pf to be able to fully replicate, but arrest prior to entering the blood by deleting a single gene. The first of our late arresting replication competent (LARC) parasites called PfSPZ-LARC1, was completely attenuated in mice with humanized livers and in humans. To increase the potential safety of PfSPZ-LARC vaccines, we created a parasite with two genes deleted, PfSPZ- LARC2, which also arrests late in the liver stage. Sanaria has also achieved in vitro production of PfSPZ, referred to as iPfSPZ, thereby eliminating the need for mosquitoes in manufacturing PfSPZ vaccines and significantly increasing efficiency and decreasing costs of producing PfSPZ vaccines. In this project we will optimize in vitro production and purification of iPfSPZ-LARC2, produce aseptic, purified, cryopreserved iPfSPZ- LARC2 and demonstrate these iPfSPZ-LARC2 are infectious, and can develop into late liver stages but are attenuated. In the next phase, we will manufacture iPfSPZ-LARC2 for assessment in clinical trials.
摘要

项目成果

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B. KIM LEE SIM其他文献

B. KIM LEE SIM的其他文献

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{{ truncateString('B. KIM LEE SIM', 18)}}的其他基金

In vitro bioreactor production of a genetically modified late liver stage-arresting replication competent Plasmodium falciparum sporozoite vaccine
体外生物反应器生产具有复制能力的转基因晚期肝阶段恶性疟原虫子孢子疫苗
  • 批准号:
    10547414
  • 财政年份:
    2022
  • 资助金额:
    $ 30万
  • 项目类别:
Expanding the breadth, magnitude, and durability of PfSPZ vaccines by creating multi-strain vaccines, designer hybrid and genetically altered parasite vaccines and use of a unique adjuvant.
通过创建多株疫苗、设计混合疫苗和转基因寄生虫疫苗以及使用独特的佐剂,扩大 PfSPZ 疫苗的广度、规模和持久性。
  • 批准号:
    10388090
  • 财政年份:
    2021
  • 资助金额:
    $ 30万
  • 项目类别:
Expanding the breadth, magnitude, and durability of PfSPZ vaccines by creating multi-strain vaccines, designer hybrid and genetically altered parasite vaccines and use of a unique adjuvant.
通过创建多株疫苗、设计混合疫苗和转基因寄生虫疫苗以及使用独特的佐剂,扩大 PfSPZ 疫苗的广度、规模和持久性。
  • 批准号:
    10598124
  • 财政年份:
    2021
  • 资助金额:
    $ 30万
  • 项目类别:
A genetically modified Plasmodium falciparum sporozoite vaccine attenuated at the late-liver stage
转基因恶性疟原虫子孢子疫苗在肝脏晚期减毒
  • 批准号:
    10603814
  • 财政年份:
    2020
  • 资助金额:
    $ 30万
  • 项目类别:
Multivalent Oral Vaccine against Enterotoxigenic Escherichia coli and Enteric Fevers
抗产肠毒素大肠杆菌和肠热病的多价口服疫苗
  • 批准号:
    9202738
  • 财政年份:
    2016
  • 资助金额:
    $ 30万
  • 项目类别:
Live Attenuated Oral Typhoid-Shigellosis Vaccine
口服伤寒志贺氏减毒活疫苗
  • 批准号:
    8903927
  • 财政年份:
    2015
  • 资助金额:
    $ 30万
  • 项目类别:
Development of Enabling Vector/Antigen Expression Technology for an Orally-Delive
用于口服给药的载体/抗原表达技术的开发
  • 批准号:
    8463454
  • 财政年份:
    2012
  • 资助金额:
    $ 30万
  • 项目类别:
Immunizing Against Malaria by Inducing Both Protective Antibodies and CD8 T Cells
通过诱导保护性抗体和 CD8 T 细胞进行疟疾免疫
  • 批准号:
    8251057
  • 财政年份:
    2012
  • 资助金额:
    $ 30万
  • 项目类别:
Multi-ligand merozoite invasion blocking malaria vaccine
多配体裂殖子侵袭阻断疟疾疫苗
  • 批准号:
    8251428
  • 财政年份:
    2012
  • 资助金额:
    $ 30万
  • 项目类别:
Development of Enabling Vector/Antigen Expression Technology for an Orally-Delive
用于口服给药的载体/抗原表达技术的开发
  • 批准号:
    8269534
  • 财政年份:
    2012
  • 资助金额:
    $ 30万
  • 项目类别:

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