Surveillance of rVSV-ZEBOV Vaccine-induced Immunity Against Ebola Virus in Previously Vaccinated Health Care Workers < EBOSURV >
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 试验地点
- 2
- 主要终点
- EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units
研究概览
简要总结
During the previous Ebola virus disease (EVD) outbreaks, the institute National de Recherche Biomédicale (INRB) and other institutional's staff in Democratic Republic of the Congo (DRC) got vaccinated with the rVSV-ZEBOV vaccine. However, the longevity of Ebola virus (EBOV)-specific immune responses after vaccination has not been studied extensively (only 1-2 years) nor comprehensively (only humoral), despite the wide use of this vaccine. With the re-emergence of Ebola in North-Kivu from a previously vaccinated individual, and the new planned vaccination campaign (considering homologous booster doses for previously vaccinated HCW) in light of the new outbreak in Beni, assessing the persistence and quality of vaccine-induced anti-EBOV immune responses is pertinent and timely.
详细描述
Despite the availability of new effective therapeutics, Ebola Virus Disease (EVD) remains a highly lethal disease, with significant collateral impact on the society. In addition, during the last decades, EVD outbreaks appear to become more and more frequent. The disease, therefore, continues to pose a significant public health concern to many areas in West and Central Africa, most notably in the Democratic Republic of the Congo (DRC), where the majority of outbreaks occur.
Fortunately, safe and effective vaccines are now available and these have become a crucial part of the current outbreak response. Most widely used in the DRC is the rVSV-ZEBOV vaccine (licensed as ErveboTM), which was recently approved for human use by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Many questions regarding EVD vaccines in general and rVSV-ZEBOV in particular remain unanswered. Currently, there is no data beyond the 2-year time point for antibody titers and more in depth investigations on IgG subclass restrictions or cellular immunity are lacking. However, previous data from non-human primate (NHP) models collectively indicate that Ebola virus (EBOV)-specific CD4+ T cells play a critical role in generating the protective antibody responses and could therefore play a vital part upon re-challenge or prove a vital predictor of poor immunity generation, durability and vaccine failure. These findings argue for an integrated and comprehensive assessment of both durable circulating nAb as well as memory CD4 T cell responses and B cell compartments to fully assess the quality of the long-lived recall responses after a single dose rVSV-ZEBOV vaccination. In addition, there are no post marketing studies that have assessed long-lived immunity outside of a clinical trial environment in routine vaccination campaigns.
Recent events have showed that acquiring such data is of the utmost importance. During the 10th EVD outbreak in DRC in North-Kivu, a person, previously vaccinated with rVSV-ZEBOV, still developed the disease and even relapsed several months later (9). These unresolved questions on the persistence of anti-EBOV immune responses are therefore highly relevant.
Due to concerns on the durability of the immune response after vaccination with rVSV-ZEBOV, a booster dose might be necessary to adequately protect front line health care workers. In this context, the INRB Goma performed a small pilot survey among their personnel, during which they found low binding antibody titers in their previously vaccinated staff (unpublished results). As in October 2021 a new EVD outbreak in North-Kivu was declared, the INRB Goma, in consultation with WHO, decided to, therefore, revaccinate some of their staff that are part of the outbreak response. This would be the first time that the rVSV-ZEBOV vaccine is administered as a booster dose, and documenting the immune response following boostering will be crucial.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
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
- •Subject is willing and able to give informed consent for participation in the study
- •Subject can be contacted by phone, email or physical address
- •Subject is aged 18 years or above
- •Subject must have a ID card (or other identification document)
- •For vaccinated group:
- •- Subject must be receiving the rVSV-ZEBOV vaccine (first or second dose) at time of inclusion OR has received a first rVSV-ZEBOV vaccine dose prior to inclusion of which vaccination date and brand is known
- •For unvaccinated group (controls):
- •Subject must NOT have received the rVSV-ZEBOV vaccine nor had any prior close contact with EBOV patients
排除标准
- •Subject was previously diagnosed with EVD
- •Subject has any contraindication to venipuncture, as determined by clinical judgement
研究组 & 干预措施
Unvaccinated participants
Participants who did received the rVSV-ZEBOV vaccine nor had any prior close contact with EBOV patients nor presenting a travel history to East DRC
Primary vaccinated participants
Participants who received a first rVSV-ZEBOV vaccine dose as part of the WHO vaccination campaign organized in Goma region (end of 2021), of which vaccination date and brand is known
Participants vaccinated < 1 year ago (from date of enrollment)
Participants who received a rVSV-ZEBOV vaccine dose less than a year prior to inclusion of which vaccination date and brand is known
Participants vaccinated 1-2 years ago (from date of enrollment)
Participants who received a rVSV-ZEBOV vaccine dose between 1-2 years prior to inclusion of which vaccination date and brand is known
Participants vaccinated 2-3 years ago (from date of enrollment)
Participants who received a rVSV-ZEBOV vaccine dose between 2-3 years prior to inclusion of which vaccination date and brand is known
Participants vaccinated > 3 years ago (from date of enrollment)
Participants who received a rVSV-ZEBOV vaccine dose > 3 years prior to inclusion of which vaccination date and brand is known
结局指标
主要结局
EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units
时间窗: Day 28
EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units (SFU) per 10\^6 cells determined by Elipot/Fluorospot assay
EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units
时间窗: Day 0
EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units (SFU) per 10\^6 cells determined by Elipot/Fluorospot assay
EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units
时间窗: Day 7
EBOV glycoprotein (GP)-specific T and B cell Spot Forming Units (SFU) per 10\^6 cells determined by Elipot/Fluorospot assay
次要结局
- Phenotypic and isotypic classification of GP-responsive T and B cells, respectively(Day 28)
- Geometric mean titers (GMT) of GP-specific IgG and neutralizing antibodies (nAb)(Day 28)
- Correlation coefficients between humoral and cellular responses(Day 28)
- Effect of age, vaccination history, comorbidities and coinfections on serological and cellular titers and on composite immune index, expressed as strong, moderate and limited immunity(Day 0)
- Seroprevalence status based on GP specific antibodies (Ab)(Day 28)
- Geometric mean titers (GMT) of GP-specific IgG and neutralizing antibodies (nAb)(Day 0)
- Geometric mean titers (GMT) of GP-specific IgG and neutralizing antibodies (nAb)(Day 7)
- Seroprevalence status based on GP specific antibodies (Ab)(Day 0)
- Seroprevalence status based on GP specific antibodies (Ab)(Day 7)
- Phenotypic and isotypic classification of GP-responsive T and B cells, respectively(Day 0)
- Phenotypic and isotypic classification of GP-responsive T and B cells, respectively(Day 7)
- Correlation coefficients between humoral and cellular responses(Day 0)
- Correlation coefficients between humoral and cellular responses(Day 7)
