07 April 2026
Press
What if all flu vaccines don't provide an equivalent response in at-risk individuals? A new French clinical study, promoted by AP-HP and coordinated by the F-CRIN-accredited clinical research networks "FORCE" and "I-REIVAC", has just been published in the international journal Clinical Infectious Diseases. The study, dubbed FLUO, shows that a new-generation influenza vaccine induces, in the short term, a greater immune response in adults living with severe obesity, with equivalent tolerance. Carried out in 15 centers in France with 206 participants, the study highlights the importance of adapting vaccine strategies to at-risk populations. It paves the way for a more personalized approach to influenza prevention.
A high-risk population still insufficiently involved in clinical trials
Severe obesity currently affects around 6% of the French adult population, or over 3 million people*, and its prevalence continues to rise. It is a recognized factor in severe forms of influenza. Yet data on vaccine efficacy in this population remain limited.
Several studies suggest that the immune response after vaccination may be less intense or less durable in people living with obesity, notably due to immune system disturbances linked to chronic inflammation. In fact, a higher immune response after vaccination, measured in particular by antibody titers (HAI), is generally associated with better protection against influenza. Although this link is not perfectly linear, numerous studies have shown that a higher antibody titer increases the likelihood of being protected against infection or of developing a less severe form of the disease.
It was to address this issue that the FLUO study was launched, with the aim of assessing whether new-generation vaccines could improve the immune response in people living with severe obesity.
Promoted by AP-HP, this study draws on the expertise of two F-CRIN-labeled clinical research networks of excellence: "FORCE", dedicated to nutrition, obesity and metabolic diseases, which federates 37 specialized obesity centers (CSOs), and "I-REIVAC", a vaccinology reference network structured around 30 clinical centers in France and backed by Biological Resource Centers (BRCs).
FLUO: a French multicenter clinical study
The FLUO study included 206 adults with severe obesity (BMI ≥ 35 kg/m2) in 15 centers in France. Participants were randomized to receive either a standard influenza vaccine or a recombinant vaccine, containing a higher amount of antigen.
Did you know? The recombinant vaccine, a new generation of vaccine
In contrast to conventional vaccines made from the influenza virus, the recombinant vaccine is designed in the laboratory to contain only one protein of the virus (hemagglutinin). This technology makes it possible to avoid using the whole virus, increase the amount of antigen, and stimulate the immune system more effectively.
Clear results: better short-term immune response
The results show that the recombinant vaccine induces a significantly higher immune response for three of the four influenza strains studied at 28 days (A/H1N1, A/H3N2, B/Yamagata), while no difference is observed for the B/Victoria strain. No tolerability problems were identified: adverse events were comparable between the two groups.
At six months, the differences between the vaccines were no longer significant, suggesting a mainly short-term benefit.
However, avenues remain open following the results of the study: FLUO is indeed an immunogenicity study and does not allow direct conclusions on the vaccine's clinical efficacy. What's more, the observed benefit seems limited in time, with no significant difference at 6 months, which could suggest a more rapid decline in the immune response in people living with obesity. These results highlight the need for further studies to assess actual clinical protection and define optimal vaccine strategies in this population.
Towards an evolution of vaccine recommendations?
These results highlight the importance of vaccine type in at-risk populations.
"FLUO's results show that a one-size-fits-all approach to influenza vaccination in at-risk individuals can no longer be considered. Adapting vaccine strategies, thanks in particular to new-generation vaccines, is a concrete way to better protect them", stresses Prof. Paul Loubet (I-REIVAC / CHU Nîmes), the study's first signatory.
In the long term, these data could help shift recommendations towards more personalized vaccine strategies. With an increase in the obese population worldwide, optimizing influenza prevention is becoming essential to reduce severe forms and hospitalizations, improve the effectiveness of vaccine campaigns and adapt strategies to patient profiles.
To remember
- People living with severe obesity are at greater risk of severe forms of influenza
- Recombinant vaccine induces stronger short-term immune response
- It has a tolerability profile comparable to the standard vaccine
- These results could lead to changes in vaccine strategies
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About the study
- Name: FLUO
- Promoteur : AP-HP
- Coordination : F-CRIN clinical research networks "FORCE" and "I-REIVAC"
- Publication: Clinical Infectious Diseases (accepted for publication)
- Design: multicenter randomized trial
*(Sources: Santé publique France, OFEO study; Inserm)
As Europe's leading university hospital center (CHU), AP-HP is at the forefront of clinical research in France. Its 38 hospitals are organized into six university hospital groups (AP-HP. Center - Université Paris Cité; AP-HP. Nord - Université Paris Cité; AP-HP. Sorbonne University; AP-HP. Université Paris-Saclay; AP-HP. Henri-Mondor University Hospitals and AP-HP. Hôpitaux universitaires Paris Seine-Saint-Denis), which have signed agreements with seven universities in the Paris region. Closely linked to major research organizations, AP-HP boasts 25 university hospital federations (FHU), 8 world-class university hospital institutes (IHU) (ICM, ICAN, IMAGINE, FOReSIGHT, SEPSIS, Institut du Cerveau de l'Enfant, reConnect, Institut de la Leucémie Paris Saint-Louis), 4 integrated cancer research sites (SIRIC) including 1 pediatric site, as well as the largest healthcare data warehouse (EDS) in France. A major player in applied research and innovation in healthcare, AP-HP holds a portfolio of 920 active patents, its clinician-researchers sign nearly 11,000 scientific publications every year, and more than 2,500 studies promoted by AP-HP are underway. In 2020, the AP-HP was awarded the Institut Carnot label, which recognizes the quality of its partnership research: the Carnot@AP-HP offers industrial players applied and clinical research solutions in the healthcare field. In addition, the AP-HP Foundation works alongside patients, caregivers and researchers for the medicine of the future, the human being at the heart of the hospital and health for all. For further information: https://www.aphp.fr
The FORCE network is the national clinical research network specializing in nutrition, obesity and associated metabolic diseases. It has been labeled an F-CRIN network of excellence since 2014. FORCE brings together French scientists with expertise in the fields of nutrition and obesity (researchers, doctors...), constituting a national collaborative organization whose aim is to develop clinical research to improve diagnosis, management as well as preventive and therapeutic strategies for obesity and associated pathologies. The FORCE network is coordinated by Professors Sébastien Czernichow and Emmanuel Disse. For further information: https://www.force-obesity.org
Created in 2007 and F-CRIN accredited since 2014, I-REIVAC evaluates vaccination and the use of monoclonal antibodies for preventive purposes in healthy volunteers and at-risk populations (immunocompromised people, the elderly, pregnant women, patients with comorbidities...). Coordinated by Professor Odile Launay and Professor Eric Tartour, the network is currently conducting over thirty vaccine clinical research projects: clinical trials (phases 1 to 4), large-scale epidemiological studies (cohorts, cross-sectional studies...) and social science work on the acceptability of vaccination programs. For further information: https://www.ireivac.org
Set up in 2012, F-CRIN (French Clinical Research Infrastructure Network) is a national platform dedicated to the development of French clinical research. It is led by Inserm in association with hospitals, healthcare industrialists and universities, and supported by the French National Research Agency and the Ministry of Health. F-CRIN's mission is to federate clinical research players in order to boost the international competitiveness and attractiveness of French research, develop the expertise of professionals by pooling know-how, resources and means, and thus accelerate the adoption of new practices and the development of new therapeutic solutions. Today, F-CRIN is based on a federative model structured around 28 components: 26 thematic research and clinical investigation networks, a multiservice platform available to sponsors and investigators to support their trials, and a national coordination unit, the infrastructure headquarters, based in Toulouse. With more than 2,000 professionals pooling their expertise and resources, F-CRIN is also the French interface for the European clinical research network ECRIN, promoting the participation of French teams and centers in multinational clinical trials. For further information: https://www.fcrin.org
Press contact:
Press department of F-CRIN and its I-REIVAC and FORCE networks: EVE'VOTREDIRCOM - 06 62 46 84 82 - servicepresse@votredircom.fr
AP-HP press department: 01 40 27 37 22 - service.presse@aphp.fr
