A new study published in Nature Immunology suggests that your age, biological sex and even your genetic makeup influence not only how many antibodies you produce during an immune response, but also which specific parts of a virus those antibodies target.
The research, led by scientists from the Institut Pasteur, CNRS and the Collège de France, provides one of the most detailed maps yet of how human antibody responses vary from person to person, findings that could have important implications for vaccine design and personalised treatments.
How age, sex and geography shape immune response?
Antibodies are central to immune defences. They are proteins produced by the immune system to recognise and neutralise viruses and other pathogens. While scientists have long understood the basic mechanisms behind antibody generation, a comprehensive model explaining how intrinsic factors such as age and sex, along with external influences like lifestyle and environment, shape human humoral responses to viruses has been lacking.
To address this gap, researchers applied a high-resolution technique known as phage immunoprecipitation sequencing. This allowed them to investigate how demographic factors, including 108 lifestyle and health-related variables, and genetic variation affect antibody reactivity to more than 97,000 viral peptides. The analysis was conducted in 1,212 healthy adults.
The team analysed data from the Milieu Intérieur study, launched 15 years ago and aimed at dissecting the interplay between genetics and environment and its impact on the immune system. One thousand healthy individuals were enrolled whose socio-economic status, lifestyle, medical history and biological markers were included in the study.
The authors “demonstrate that age, sex and continent of birth extensively affect not only the viruses but also the specific viral epitopes targeted by the antibody repertoire.”
“A major strength of this study is its exhaustive quantification of the antibody repertoire. We were able to characterise exactly which parts of viral proteins are targeted by antibodies in each individual,” author Etienne Patin, research director in the human evolutionary genetics laboratory at the Institut Pasteur, said in the press release.
One of the most striking findings was the impact of age. The researchers found that more than half of the antibody repertoire produced as part of an immune response varied depending on age. For influenza H1N1 and H3N2, antibodies in young adults were found to mainly target a part of the viral surface protein known as hemagglutinin, which evolves rapidly. In contrast, antibodies among older individuals tended to target a more stable region of the same protein known as the stalk domain.
This distinction is important because rapidly evolving viral regions can change from season to season, potentially reducing vaccine effectiveness, whereas conserved regions remain more stable across viral strains. The shift in antibody targeting with age could therefore influence how different age groups respond to infections and vaccines.
Biological sex also played a significant role. Women were found to produce more antibodies against hemagglutinin, while antibodies among men tended to target other viral proteins, despite comparable vaccination rates between the two sexes. These findings highlight inherent biological differences in immune responses that extend beyond behavioural or exposure-related factors.
Geography further shaped immune patterns. The study was extended to include an African cohort, revealing that for a given virus such as the Epstein-Barr virus, antibodies can recognise varied viral proteins depending on the geographical and epidemiological context. This suggests that local exposure histories and environmental pressures influence how immune systems prioritise viral targets.
Genes and immunity
Beyond age, sex and geography, host genetic factors emerged as powerful determinants of antiviral immunity. “Furthermore, we identify strong associations between antibodies against 34 viruses and genetic variants at HLA, FUT2, IGH and IGK loci, some of which increase autoimmune disease risk,” the authors said.
“We identified mutations in genomic regions known to encode the immunoglobulin repertoire. These variants determine which genes are used to produce antibodies,” Patin said.
These findings indicate that genetics not only influence whether antibodies are produced, but also determine which antibody genes are selected during an immune response. This genetic imprinting shapes the architecture of the antibody repertoire, potentially affecting vulnerability to infections and responsiveness to vaccines.
The discovery that certain immune response patterns are linked to genetic variants associated with autoimmune disease risk also raises important questions about the delicate balance between effective antiviral defence and immune overactivity. Understanding this relationship could help scientists better predict which individuals may be more prone to immune-related disorders.
Study limitations and future scope
The researchers noted several limitations. The VirScan library, while broad, captures only linear peptides and may miss antibodies that recognise conformational epitopes. Antibody cross-reactivity may also blur virus-specific responses, and although AVARDA was used to reduce this risk, it may introduce false negatives. They added, “the large number of tests required to analyse the full viral peptidome, combined with the cohort size, may further increase the false negative rate.”
Importantly, “PhIP-seq does not determine whether antibodies are protective against viral infection, which requires dedicated experiments.” The authors also stressed that demographic and genetic factors explain only part of the variation observed, noting that “Longitudinal studies integrating the human viral exposome and virome… are needed to fully elucidate the determinants of human variation in humoral responses to viruses.”
Despite these constraints, the team said the study offers high-resolution insight into how age, sex, continent of birth and genetics shape antibody targeting, with potential implications for vaccine and therapeutic strategies.
This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS
