## Protocol Section
### Identification Module
**NCT ID:** NCT06432855

**Acronym:** GEDIPOP

**Brief Title:** Genetic Determinants of the Antiviral Immune Response in Oceanian Populations

**Official Title:** Genetic Determinants of the Antiviral Immune Response in Oceanian Populations

#### Organization Study ID Info
**ID:** 2022-035
#### Organization
**Class:** INDUSTRY
**Full Name:** Institut Pasteur
#### Secondary ID Infos
**Domain:** ID RCB
**ID:** 2023-A02206-39
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2027-12-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-06-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-15

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-22
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Institut Pasteur

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Oceania's populations, including Melanesians, are paying a heavy price for dengue fever, which has been circulating actively in the region since the Second World War. In New Caledonia (NC), the incidence of dengue fever is higher among municipalities predominantly populated by Melanesians, suggesting that Melanesians may have an increased susceptibility to symptomatic dengue fever. Differences in antiviral immune responses between populations of different geographical origins are partly the result of population-specific immune regulatory variants. In turn, viruses have imposed considerable selective pressure on human populations. Although crucial to understanding their susceptibility to viral infections, the genetic determinants of the antiviral immune response of Oceanians remain to be characterized.

In this context, we hypothesize that the genetic origin of Oceanians, and Melanesians in particular, has shaped their antiviral immune response and contributes to their greater susceptibility to certain viral infections. We aim to characterize the immune response to pathogens affecting the New Caledonian population, and in particular to dengue virus, of Melanesian and European populations, and to identify its genetic determinants. We will also explore whether saliva can be used as a non-invasive sample to study the seroprevalence of dengue in Oceanian populations.

**Detailed Description:** Cross-sectional observational study with prospective sample and data collection Individuals will be identified from among eligible participants in the STEP-BSA21 and COVCAL studies.

Information and consent Questionnaire, saliva collection on Oragene tube, buccal swabbing and 20 mL blood collection on CPT tube

DNA extraction and low-coverage sequencing of participants' complete genomes And Isolation and in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with dengue virus

* single-cell RNA sequencing (scRNAseq)
* multiplex quantification of cytokines and chemokines
* bioinformatics analysis to identify genetic markers associated with a differential transcriptomic and secretory response to dengue virus stimulation.

### Conditions Module

**Conditions:**

- Virus

**Keywords:**

- dengue

- immunity

- genetics

- Ocenian populations

- New Caledonia

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 220

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Saliva samples and 20 mL blood samples from individuals of Melanesian and European origin from NC

**Intervention Names:**

- Other: Blood collection

- Other: saliva collection

**Label:** Non-febrile adults of Melanesian and European origin

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Non-febrile adults of Melanesian and European origin

**Description:** 20 ml-blood sample

**Name:** Blood collection

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Non-febrile adults of Melanesian and European origin

**Description:** saliva sample

**Name:** saliva collection

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Identification by genomic techniques of expression Quantitative Trait Loci (eQTL) specifically associated with the innate immune response of Peripheral Blood Mononuclear Cells (PBMCs) collected from individuals of Melanesian and European origin and stimulated in vitro by DENV.

**Measure:** Identify the genetic determinants of the innate immune response to pathogens affecting the New Caledonian population, and in particular to the dengue virus in individuals of Melanesian and European origin.

**Time Frame:** 3 years

#### Secondary Outcomes

**Description:** Low-coverage DNA sequencing of the complete genome of individuals of Melanesian and European origin.

**Measure:** To describe the genetic diversity of Melanesian and European populations in NC in relation to the determinants of susceptibility to health problems affecting NC populations.

**Time Frame:** 3 years

**Description:** Quantification by single cell RNAseq techniques of differentially expressed transcripts in response to in vitro dengue virus stimulation by Peripheral Blood Mononuclear Cells (PBMCs) collected from individuals of Melanesian and European origin.

**Measure:** Characterizing the transcriptomic response to DENV in individuals of Melanesian and European origin.

**Time Frame:** 3 years

**Description:** Quantification by multiplex techniques of the concentration of cytokines and chemokines differentially secreted in response to in vitro stimulation by dengue virus by Peripheral Blood Mononuclear Cells (PBMCs) collected from individuals of Melanesian and European origin.

**Measure:** Characterize the cytokine and chemokine response to DENV in individuals of Melanesian and European origin.

**Time Frame:** 3 years

**Description:** Quantification by multiplex techniques of the concentration of cytokines and chemokines differentially secreted in response to in vitro stimulation by dengue virus by Peripheral Blood Mononuclear Cells (PBMCs) collected from individuals of Melanesian and European origin.

Multivariate analyses of the association of environmental factors collected during the inclusion visit (questionnaire and measurements) or during analyses conducted as part of the present research with the immune response targeting the dengue virus.

**Measure:** Study the effect of environmental factors (smoking/non-smoking status, history of Cytomegalovirus or dengue virus infection, presence of diabetes, etc.) on the immune response to dengue virus.

**Time Frame:** 3 years

**Description:** Next-generation sequencing and analysis of the oral microbiome on a saliva sample

**Measure:** Study the oral microbiome of individuals of Melanesian and European origin and analyze its association with the immune response to pathogens.

**Time Frame:** 3 years

**Description:** Luminex quantification of dengue virus antibodies in serum and saliva from Melanesian and European individuals.

**Measure:** Determine whether history of dengue virus infection can be demonstrated by testing saliva for antibodies using the Luminex technique.

**Time Frame:** 3 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Adult
* Non-febrile
* Self-declared member of the Melanesian or European community
* Having given consent to participate in the study

Exclusion Criteria:

* People who have taken part in a clinical study in the last 6 months in which they were exposed to a health product as part of the investigation (pharmaceutical product or device or placebo).
* People taking part in an ongoing clinical study
* People declaring themselves to belong to two communities (e.g. people of mixed European and Melanesian descent)
* Pregnant and breast-feeding women (in whom the immune response could be modified)
* People with a long-term medical condition (as defined by the French social security system) that could have an effect on the immune response, excluding dengue risk factors prevalent in New Caledonia such as diabetes, overweight/obesity and hypertension.
* Individuals with an acute infection (viral, bacterial or fungal) within 3 months of inclusion.
* Chronic administration (for more than 14 days) of immunosuppressants or treatments affecting the immune system in the 6 months prior to inclusion. For corticosteroids, this corresponds to a dose equivalent to 20 mg/day of prednisone or equivalent for more than two weeks (inhaled or topical steroids are permitted).
* Administration of a vaccine within 3 months prior to inclusion.
* Administration of blood products or immunoglobulins within 3 months of inclusion.
* People with known allergies to antibiotics, which could have an impact on the in vitro culture of PBMCs in the presence of antibiotics
* Persons not intellectually capable of answering the questionnaire
* Persons under guardianship, curatorship or any other legal incapacity

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** cinizan@pasteur.nc

**Name:** Catherine Inizan, PhD

**Phone:** +687 27 26 66

**Role:** CONTACT

**Contact 2:**

**Email:** mdupont@pasteur.nc

**Name:** Myrielle Dupont-Rouzeyrol, PhD

**Phone:** +687 27 75 30

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Nouméa

**Contacts:**

***Contact 1:***

- **Name:** Marc Jouan, MD

- **Role:** CONTACT

**Country:** New Caledonia

**Facility:** Institut Pasteur de Nouvelle-Calédonie

**Zip:** 98 835

#### Overall Officials

**Official 1:**

**Affiliation:** Institut Pasteur de Nouvelle-Calédonie

**Name:** Marc Jouan, MD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M6913

- Name: Dengue

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T1794

- Name: Dengue Fever

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
