Innovative study led by the InnoHK Centre for Immunology & Infection characterizes immune variability in a healthy Asian population

The Healthy Human Global Project - Hong Kong : a community-based cross-sectional study of a healthy Asian population

The InnoHK Centre for Immunology & Infection (InnoHK C2i), established through a strategic partnership between The University of Hong Kong (HKU) and the Institut Pasteur,  together with the Institut Pasteur Milieu Interieur (MI), FAMILY Cohort (HKU, School of Public Health)  and the Centre for Sports and Exercise (HKU CSE) have established  the Healthy Human Global Project–Hong Kong (HHGP‑HK), a rigorously characterized cohort of 1,025 healthy adults aged 20–79, balanced by sex and designed to serve as a long‑term resource for understanding immune variability in East Asian populations. The findings, published in Cell Reports Medicine, address a critical global gap in biomedical research that has historically focused on populations of European ancestry.

InnoHK C2i and HKU have established the Healthy Human Global Project–Hong Kong (HHGP‑HK), a rigorously characterized cohort of 1,025 healthy adults aged 20–79, balanced by sex and designed to serve as a long‑term resource for understanding immune variability in East Asian populations.

Most large‑scale immunology and health studies have been conducted in Europe or the United States, creating a systemic bias in biomedical reference data. This limits the accuracy of health metrics, disease risk scores, and aging biomarkers when applied to non‑Western populations.

The HHGP‑HK study directly addresses this issue by:

• Establishing Asian‑specific immune and clinical reference data

• Enabling direct comparison with the well‑known French Milieu Intérieur cohort

• Demonstrating that widely used health and biological aging scores may not fully translate across populations

Between July 2022 and September 2023, participants were recruited across Hong Kong using strict physical and mental health criteria to ensure the cohort reflected immune function outside of disease contexts. Each participant underwent comprehensive clinical laboratory testing, detailed lifestyle and mental health assessments, immune and biological sampling, and, for a large subset, continuous monitoring using wearable fitness devices. This integrated approach allowed researchers to examine immune and physiological variability through the combined lenses of biology, behavior, and environment.

Analyses revealed widespread and statistically significant effects of age and sex across clinical laboratory measures, including immune cell counts, blood pressure, lipids, kidney markers, and liver enzymes. Many of these patterns were consistent with those observed in European cohorts, confirming shared biological trajectories across populations. However, important differences were also identified.

Notably, levels of C‑reactive protein, a widely used marker of systemic inflammation, were lower in healthy Hong Kong participants compared with their French counterparts, consistent with prior observations of ancestry‑related differences in baseline inflammation. Variability in liver enzymes also differed between cohorts, with greater variance observed among European donors, suggesting the influence of environmental or lifestyle factors such as diet or alcohol consumption.

When commonly used composite health metrics were applied, divergent performance was observed. While the Framingham 10‑year cardiovascular risk score behaved similarly across populations, the PhenoAge biological aging score—developed using Western datasets—produced systematically different aging trajectories in Asian participants. In particular, women in the Hong Kong cohort appeared biologically younger than predicted by the model, raising important questions about the cross‑population validity of aging biomarkers.

“This is a critical first milestone for the HHGP-HK project and our goal to understand the causes of immune variability in healthy Asian populations. In this initial comparison with our existing healthy French cohort, Milieu Interieur we already see that at the broad clinical level the two healthy populations are quite similar, but with some notable differences. However ongoing work is identifying important differences in terms of specific immune responses which this cohort will help us understand in the coming years” said Dr Darragh Duffy, Principal Investigator, InnoHK C2i, Director of the Translational Immunology Unit and Co-coordinator of the LabEx Milieu Interieur project at the Institut Pasteur.

By establishing a deeply phenotyped healthy Asian cohort, the HHGP‑HK study lays essential groundwork for future research into gene–environment interactions, immune aging, and precision medicine. The findings underscore the importance of validating clinical reference ranges and predictive health scores across diverse populations, particularly as such tools are increasingly used in preventive medicine and public health.

The HHGP‑HK cohort forms part of the broader Healthy Human Global Project, an international effort to expand immune reference data worldwide and ensure that biomedical advances are informed by global human diversity.

o   Link to the publication:

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00118-7

Funding and Acknowledgements

This research was funded by InnoHK, an initiative of the Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region, with additional support from the FAMILY Cohort and collaborating institutions.

About the research team

The research is led by Dr Darragh Duffy, Principal Investigator, InnoHK C2i, Director of the Translational Immunology Unit and Co-coordinator of the LabEx Milieu Interieur project and Professor James Di Santo, Principal Investigator, InnoHK C2i and Director of the Innate Immunity Unit, Université de Paris, Inserm U1223, both at Institut Pasteur, Paris. The study recruitment was coordinated by Dr Michael Ni, Clinical Associate Professor and Programme Director of the FAMILY Cohort in the School of Public Health, HKUMed and Mr Wilson Ng, Project Manager at InnoHK C2i.

The clinical implementation was executed by Dr Rex Hung, Principal Medical Consultant, InnoHK C2i and Honorary Assistant Professor in the School of Public Health, HKUMed. Other research team members of this study included Dr Michael Tse, Director of Centre for Sports and Exercise, HKU and Mr Glen Joe, Exercise Physiologist of Centre for Sports and Exercise, HKU.

About the InnoHK Centre for Immunology & Infection (InnoHK C2i)

The InnoHK Centre for Immunology & Infection is the fruit of a long-standing partnership of more than 20 years between the LKS Faculty of Medicine of the University of Hong Kong and the Institut Pasteur, two major institutions combining their expertise to establish this centre of excellence. Within the InnoHK initiative, InnoHK C2i adopts innovative strategies to identify and contain emerging infectious diseases and transform Hong Kong and the Greater Bay Area into a global hub of knowledge and research.

InnoHK C2i’s work is centered around four major research programs to face public health challenges and make Hong Kong a global center of excellence for precision medicine population strategies and innovative interventions targeting emerging infectious diseases. They aim to characterise immune responses to infectious agents and their components in a healthy Asian population and develop new vaccine platforms for influenza, new strategies for mosquito-borne viruses and new treatments for lethal respiratory virus infections.

Website: https://www.c2i.hk

About the FAMILY Cohort (School of Public Health, HKUMed)

The FAMILY Cohort is a territory-wide longitudinal cohort study that seeks to understand the physical, mental and social wellbeing at the individual, household, and neighbourhood level in Hong Kong by the School of Public Health, LKS Faculty of Medicine of The University of Hong Kong. The establishment of the original cohort was funded by the Hong Kong Jockey Club Charities Trust from 2007 to 2014.

Website: https://familycohort.sph.hku.hk/en/

About The Institut Pasteur

A non-profit foundation established in 1887 by Louis Pasteur, the Institut Pasteur is a world-class biomedical research center dedicated to studying and combating disease, particularly infectious diseases. From the invention of the rabies vaccine to the identification of HIV and the discovery of messenger RNA, some of the most significant breakthroughs in modern biomedical science were achieved here. The excellence of Pasteur’s research has been recognized with 10 Nobel Prizes in physiology or medicine.

The Institut Pasteur employs more than 3,100 stab members representing nearly 100 nationalities, including 1,700 scientists and engineers. Its Paris campus hosts hundreds

of researchers from other organizations, notably Inserm and the CNRS, and it collaborates with numerous leading international research institutions, including EMBL, the University of Oxford, the Francis Crick Institute, Rockefeller University and UCSF.

A member of a network of more than 30 institutes across five continents- the Pasteur Network- and host to nearly ten WHO Collaborating Centres, the Institut Pasteur works on the ground alongside communities to advance public health worldwide.

Website: https://www.pasteur.fr/en

About Milieu Intérieur (the Institut Pasteur)

The Milieu Intérieur (MI) project, coordinated by Dr Darragh Duffy and Prof Lluis Quintana-Murci at the Institut Pasteur, Paris was established in 2011 with the aim to define the parameters that characterise a healthy immune response and its natural variation across individuals, and in doing so, inform clinical strategies for managing disease. For this, 1000 healthy volunteers (1:1 sex ratio; stratified across 5 decades of life from 20 to 69 years of age) were recruited. For each individual, a detailed eCRF of lifestyle and demographic variables, whole blood for immune phenotyping, immune stimulation and genomic analysis, as well as faecal samples and nasal swabs for metagenomic studies of microbiota, were collected. Punch skin biopsies were also taken to generate primary fibroblast lines and iPSc (from selected donors) to enable mechanistic studies. The MI project has provided a definition of protein and transcriptional immune signatures for healthy immune responses. The project also revealed new insights into the genetic and non-genetic factors driving immune response variation. In addition to key fundamental insights, the MI project has established a rich sample repository and data-warehouse, supporting ongoing integrative research in systems immunology.

Website: https://www.milieuinterieur.fr/en/

About the Centre for Sports and Exercise (The University of Hong Kong)

The Centre for Sports and Exercise (CSE) manages HKU’s sports facilities and promotes physical activity among students, staff, alumni, and the wider community to enhance health and wellbeing. It oversees indoor campus facilities and outdoor amenities at the Stanley Ho Sports Centre in Sandy Bay. CSE also operates fitness centers, including the conveniently located ‘HKU B-Active,’ which houses the flagship Active Health Clinic established in 2009 to support physical, mental, and social health through service programs and academic collaborations. Additionally, CSE supports university athletes in achieving sporting excellence and success in inter-university competitions.

Website: https://cse.hku.hk

Media enquiries:

InnoHK Centre for Immunology & Infection (InnoHK C2i)

Simon Muller (Tel: 6194 7531 | Email: simon.muller@c2i.hk)