Genetic Determinants of the Antiviral Immune Response in Oceanian Populations
ConditionVirus
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitut Pasteur
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Adult
Non-febrile
Self-declared member of the Melanesian or European community
Having given consent to participate in the study
Disqualifiers
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)
Trial design
Design model
Single group
Treatments tested in this trial
Blood collection
Other intervention20 ml-blood sample
saliva collection
Other interventionsaliva sample
Treatment groups
220 Participants
are divided into 1 treatment groupGroup A: Non-febrile adults of Melanesian and European originOther 2 interventions
Trial outcomes
Primary outcomes
1
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 yearsSecondary outcomes
1
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 years2
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 years3
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 years4
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 yearsSponsors and contacts
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Source ClinicalTrials.gov
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