Genetic Determinants of the Antiviral Immune Response in Oceanian Populations

N/ANot Yet RecruitingNCT06432855

Institut Pasteur220 enrolled

Overview

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, the hypothesis is 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. The aim is 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. It will be explored whether saliva can be used as a non-invasive sample to study the seroprevalence of dengue in Oceanian populations.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

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.

Time frame: 3 years

Secondary Outcomes

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.

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

Time frame: 3 years

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

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.

Time frame: 3 years

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

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.

Time frame: 3 years

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.

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.

Time frame: 3 years

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

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

Time frame: 3 years

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

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

Time frame: 3 years

Genetic Determinants of the Antiviral Immune Response in Oceanian Populations

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts