Circulating biomarkers play a central role in translational research and precision medicine, particularly for the diagnosis, prognostic, monitoring of inflammatory or infectious diseases and patient stratification. Advances in analytical technologies enable standardised, sensitive and multiplexed assays, but their application remains limited by the lack of reliable reference values derived from well-characterised healthy populations. Indeed, the available data are often heterogeneous and difficult to transfer between platforms.

In this context, the establishment of institutional reference cohorts appears essential for the correct interpretation of immunological parameters-which could be strongly influenced by demographic and clinical factors-and for defining relevant cut-off values when identifying new biomarkers of interest. This issue is particularly critical in the field of viral respiratory infections, where current diagnostic approaches still have several limitations.

Circulating biomarkers play a central role in translational research and precision medicine, particularly for the diagnosis, prognostic, monitoring of inflammatory or infectious diseases and patient stratification. Advances in analytical technologies enable standardised, sensitive and multiplexed assays, but their application remains limited by the lack of reliable reference values derived from well-characterised healthy populations. Indeed, the available data are often heterogeneous and difficult to transfer between platforms.

In this context, the establishment of institutional reference cohorts appears essential for the correct interpretation of immunological parameters-which could be strongly influenced by demographic and clinical factors-and for defining relevant cut-off values when identifying new biomarkers of interest. This issue is particularly critical in the field of viral respiratory infections, where current diagnostic approaches still have several limitations.

Diagnosis is usually based on PCR tests targeting the DNA or RNA of pathogens, requiring a virus-specific test. In practice, only a few viruses (SARS-CoV-2, RSV, influenza) are tested for as a first-line investigation, whilst many other agents may be involved. As a comprehensive approach is difficult to achieve, viral infections often remain under-reported.

Furthermore, the detection of a virus by PCR may indicate either an active infection or residual traces of a past infection. Although viral load can aid interpretation, it does not always allow for a definitive conclusion, making it difficult to distinguish between ongoing viral replication and the persistence of genetic material. It is therefore necessary to have additional markers associated with active infection.

In this context, analysing the host response represents a promising alternative. Viruses induce, in particular, the production of type I interferons (IFN-I), the measurement of which could point the diagnosis towards a viral origin and reflect ongoing infectious activity. However, the interpretation of these biomarkers requires robust reference standards, taking into account their variability across individuals and contexts.

Several studies illustrate the value of such approaches, such as the REFIPA study (NCT07239830), conducted in subjects over 80 years of age, which aims to characterise the immune response, particularly IFN-I, in the context of immunosenescence. This type of study highlights the need for well-phenotyped healthy ? control populations according to age groups and clinical contexts.

Finally, beyond the creation of reference databases, the development of biobanks appears essential. This would enable the establishment of harmonised and directly usable reference values, thereby facilitating translational, basic and pre-clinical research projects, as well as the identification and validation of new biomarkers.

Inclusion Criteria:

• Participants aged between 18 and 65 years (inclusive)
• Participants with no known medical conditions
• Body weight of 50 kg or more

Exclusion Criteria:

• Participants with symptoms of an active infection (symptom questionnaire or temperature > 37.5°C).

  • Subjects participating in another interventional study with an exclusion period that is still ongoing or that may interfere with this protocol
  • Pregnant women, women in labour or breastfeeding women
  • Individuals deprived of their liberty by a judicial or administrative decision
  • Individuals receiving psychiatric care
  • Individuals admitted to a health or social care facility for purposes other than research
  • Adults subject to legal protection measures (guardianship, curatorship)
  • Individuals not affiliated with a social security scheme or beneficiaries of a similar scheme