Characterization of Adaptive Immune Responses to Oropouche Virus (OROV) Infection (OROV-IMM)
Oropouche virus (OROV), a re-emerging South American arbovirus causing dengue-like fever and occasional neurological complications, is expanding its circulation towards more densely populated areas in French Guiana, as evidenced by recent cases near Cayenne in 2026. While animal models indicate that B cell-mediated humoral immunity is critical for viral control, the human antibody response to OROV remains poorly characterized. Despite WHO-led international research efforts, there is currently no vaccine, antiviral treatment, or described human monoclonal antibody against OROV - a major gap that hinders therapeutic and vaccine development. Identifying human neutralizing monoclonal antibodies could offer a promising therapeutic option, particularly for vulnerable populations such as pregnant women.
研究概览
详细说明
The goal of this project is to characterize the adaptive immune response to OROV infection during the convalescent phase.
The study is based on three complementary populations: (1) 17 adults with confirmed past OROV infection (2020) who will be recontacted for follow-up sampling; (2) 50 adults recruited prospectively from a village with ∼80% seroprevalence, aiming to include at least 20 seropositive individuals for robust analysis of antigen-specific B and T cell responses; and (3) an exploratory cohort of 1 to 10 newly confirmed OROV cases identified during the study period in the Cayenne region, enrolled during the convalescent phase (≥1 month post-diagnosis) to complement the immunological analyses conducted in the first two populations.
A 20 ml blood sample is collected, along with data collection (mainly health data), at the time of enrollment.
The study involves: (1) confirming past OROV infection by detecting OROV-specific polyclonal antibodies in plasma; and (2) characterizing OROV-specific B and T cell responses. Key methodological steps include: isolation of OROV-specific B cells by flow cytometry followed by single-cell culture and stimulation to generate human monoclonal antibodies; screening of secreted mAbs against OROV antigens combined with VDJ sequencing to characterize immunoglobulin repertoires; and structural characterization of neutralizing mAbs using cryo-electron microscopy and nano-imaging to identify conserved epitopes.
研究类型
注册 (估计的)
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
The study population lives in French Guiana in 3 different areas (Saül, Trois Sauts, and Cayenne and its surroundings), and eligible individuals (Populations 1 and 3) or those residing in a high-seroprevalence geographic area (Population 2) were identified by the National Reference Center (CNR) for Arboviruses at the Institut Pasteur of French Guiana (IPG) as part of arbovirus virological surveillance in French Guiana.
描述
Inclusion Criteria:
For all:
- Adults (≥18 years old)
- Willingness to participate in the study after explanation and signing of the informed consent form
Study population 1:
- Presenting a laboratory-confirmed OROV infection, defined by a positive real-time RT-PCR and/or positive seroneutralization performed as part of the management of and response to the 2020 OROV epidemic in Saül.
Study population 2:
- Residing in Trois-Sauts for at least 5 years
Study population 3:
- Presenting a laboratory-confirmed OROV infection, defined by a positive real-time RT-PCR and/or positive seroneutralization, identified in the Cayenne area and surrounding localities during the study period, as part of the surveillance activities of the CNR for Arboviruses (IPG).
Exclusion Criteria:
For all:
- Pregnant women.
- Individuals presenting with severe chronic pathologies (notably active cancer, primary or secondary immunodeficiency, immunosuppressive treatment, HIV infection, or autoimmune diseases), according to the information declared by the participants.
学习计划
研究是如何设计的？
设计细节
- 观测模型：OTHER
- 时间观点：PROSPECTIVE
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
adults with confirmed past OROV infection (2020) recruited from Saül
|
A 20-ml blood sample |
|
adults recruited from Trois-Sauts with ∼80% seroprevalence
|
A 20-ml blood sample |
|
newly confirmed OROV cases identified during the study period in the Cayenne region
|
A 20-ml blood sample |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Characterization of the adaptive immune response to OROV infection during the convalescent phase.
大体时间：12 months
|
OROV-specific polyclonal antibodies will be detected in participants' plasma to confirm prior infection. |
12 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Isolate OROV-specific B cells (recognizing the Gn_Gc antigenic complex) and generate human monoclonal antibodies by single B cell culture.
大体时间：12 months
|
Isolation of OROV-specific B cells by flow cytometry, followed by culture and stimulation of single B cells to generate and identify human monoclonal antibodies specific to OROV. |
12 months
|
|
Screening of secreted mAbs using OROV antigens and VDJ sequencing to characterize immunoglobulin repertoires.
大体时间：12 months
|
secreted mAbs using OROV antigens and VDJ sequencing will be screened to characterize immunoglobulin repertoires. |
12 months
|
|
Structural characterization of neutralizing mAbs by cryo-EM and nano-imaging to identify conserved epitopes.
大体时间：12 months
|
cryo-EM and nano-imaging will be performed on neutralizing mAbs to characterize structurally the mAbs |
12 months
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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