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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Bemonsteringsmethode
Studie Bevolking
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.
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Observatiemodellen: OTHER
- Tijdsperspectieven: PROSPECTIVE
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
|---|---|
|
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 |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Characterization of the adaptive immune response to OROV infection during the convalescent phase.
Tijdsspanne: 12 months
|
OROV-specific polyclonal antibodies will be detected in participants' plasma to confirm prior infection. |
12 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Isolate OROV-specific B cells (recognizing the Gn_Gc antigenic complex) and generate human monoclonal antibodies by single B cell culture.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 12 months
|
cryo-EM and nano-imaging will be performed on neutralizing mAbs to characterize structurally the mAbs |
12 months
|
Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 2026-047_OROV-IMM
- 2026-A01467-44 (Andere identificatie: ID-RCB)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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