An Open-label Interventional Study to Understand and Quantify the Duration of Humoral Immunological Memory to a Single Dose of Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Ebola-specific Antibody Titers
研究概览
简要总结
In this study 30 healthy adult participants will receive a single dose of an Ebola vaccine. Blood samples, fine needle aspirates, core biopsies, and bone marrow aspirates will be collected prior to and following vaccination to assess immune responses in the blood, lymph nodes, and bone marrow over multiple time points.
详细描述
Ebolaviruses (EBOV), cause Ebola Virus Disease, a condition characterized primarily by hemorrhagic fevers with remarkably elevated mortality rates. The genus Ebolavirus encompasses five distinct viral species, namely Bundibugyo virus (BDBV), Zaire Ebola virus (ZEBOV), Reston virus (RESTV), Sudan virus (SUDV), and Taï Forest virus (TAFV).
More than 20 human outbreaks have been reported world-wide since the identification of EBOV in the late 1970s. The most common geographical region affected by EBOV outbreaks is Central Africa, with two of the most notable outbreaks occurring in Kikwit, Democratic Republic of Congo in 1995, and Gulu, Uganda in 2000. Outside of Africa, EBOV infections have been reported in countries like Philippines, Italy, United Kingdom, United States of America, and others. Of particular significance is the 2014-2016 West African ZEBOV outbreak, which is known as the most extensively recorded outbreak to date with over 28,000 reported infections and a 40% approximated mortality rate. The outbreak significantly surpassed all preceding ZEBOV outbreaks in terms of geographical coverage, number of impacted individuals, and its disruptive influence on conventional societal activities.
Fatal ZEBOV infection is characterized by flu-like symptoms and high fever followed by multi-organ failure. While case-fatality rates vary between outbreaks and among the Ebola viruses, ZEBOV has been associated with up to 90% lethality. While specific treatment strategies including convalescent plasma, monoclonal antibodies, and/or direct- acting antiviral agents are being pursued, it is unlikely that treatment directed at the individual will be sufficient to control outbreaks. Hence, it is important to investigate prophylactic vaccines that confer protection against Ebola viruses in at-risk populations to prevent future outbreaks. Understanding the durability of these vaccines is of paramount importance.
The recombinant vesicular stomatitis virus-based Ebola vaccine (rVSVΔG-ZEBOV-GP) was approved in 2019 as a single dose in the prevention against Ebola virus disease (EVD). Protection is primarily conferred by antibodies targeting the ZEBOV glycoprotein (GP), and ZEBOV-GP Immunoglobulin G (IgG) memory B cells (MBCs) can be detected in the blood 6 months following vaccination.
It is not fully understood, however, whether a single dose of rVSVΔG-ZEBOV-GP effectively generates germinal center (GC) responses that result in durable immunological memory.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent for study.
- •For women of childbearing potential: willing to engage in effective methods of contraception starting at least 28 days prior to vaccination and during the study.
- •Willing to minimize blood and body fluid exposure to others (encourage abstinence, and hand hygiene; discourage contact with blood, vomit, feces without personal protective equipment (PPE) for at least 14 days following vaccine administration.
- •Willing to forgo blood donation 30 days prior to and for the duration of study participation.
排除标准
- •At risk of travel-related or occupational exposure to Ebola virus such as through laboratory, clinical contact, field work, or in the judgment of the investigator.
- •Received any Ebola vaccines or have history of Ebola Virus Disease (EVD).
- •Current or previous diagnosis of immunocompromising condition such as human immunodeficiency virus or other immunosuppressive condition by receiving systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (for corticosteroids: ≥ 10mg/day of prednisone or equivalent) or anticipates the need for immunosuppressive treatment at any time during participation in the study.
- •Pregnant and/or breastfeeding (must have urine pregnancy test on the day of vaccination and during screening visit)
- •Known allergy to any component of the rVSV∆G-ZEBOV-GP vaccine products (VSV, albumin, tris, rice protein).
- •History of severe local or systemic reactions to any vaccination.
- •Received investigational drug within 5 half-lives or 28 days, whichever is longer, prior to study vaccination.
- •Received or intends to receive vaccines within 28 days prior to or following study vaccination.
- •Received immunoglobulins and/or any blood products within 120 days prior to study vaccination.
- •Clinical evidence of systemic infection or other acute intercurrent illness (e.g. oral temp >38°C or > 100.4°F) less than 72 hours prior to study vaccination.
- •Currently has symptomatic, acute, or unstable chronic disease requiring medical or surgical care, to include significant change in therapy or hospitalization, at the discretion of the investigator.
- •History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions, or occupational conditions that in the opinion of the investigator would preclude compliance with the study.
- •Any condition that would limit the ability of the participant to meet protocol requirements or would place the participant at unreasonable risk in the opinion of the investigator.
研究组 & 干预措施
Recombinant Vesicular Stomatitis Vaccine for Ebola
Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP).
干预措施: Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) (Biological)
Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 14 Days
Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) plus deuterium labeled water three times daily for 14 days from days 1-15.
干预措施: Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) (Biological)
Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 14 Days
Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) plus deuterium labeled water three times daily for 14 days from days 1-15.
干预措施: Deuterium Labeled Water (Other)
Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 28 Days
Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) plus deuterium labeled water three times daily for 28 days from days 57-85.
干预措施: Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) (Biological)
Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 28 Days
Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) plus deuterium labeled water three times daily for 28 days from days 57-85.
干预措施: Deuterium Labeled Water (Other)
结局指标
主要结局
Ebola-specific Antibody Titers
时间窗: Day 29, Day 366
Antibody titers are examined by direct comparison of antibody titers in the blood. Serum-binding Ebola-specific antibody titers following rVSV∆G-ZEBOV-GP vaccination will be measured by Enzyme-Linked Immunosorbent Assay (ELISA).
次要结局
- Severity of Adverse Events(Up to Day 28)
- Frequency of Adverse Events Related to Bone Marrow Aspiration(Up to Day 366)
- Frequency of Serious Adverse Events(Up to Day 366)
- Frequency of Adverse Events Related to Fine Needle Aspiration/Biopsy of Lymph Node(Up to Day 366)
- Frequency of Adverse Events (AEs)(Up to Day 28)
- Severity of Adverse Events Related to Fine Needle Aspiration/Biopsy of Lymph Node(Up to Day 366)
- Severity of Adverse Events Related to Bone Marrow Aspiration(Up to Day 366)