Nat Commun . Adjuvanted influenza vaccination increases pre-existing H5N1 cross-reactive antibodies

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Nat Commun


. 2026 Jan 7.
doi: 10.1038/s41467-025-68137-x. Online ahead of print. Adjuvanted influenza vaccination increases pre-existing H5N1 cross-reactive antibodies

Mariana Alcocer Bonifaz ¹ , Disha Bhavsar ^{2 3} , Claire-Anne Siegrist ¹ , Arnaud Didierlaurent ¹ , Benjamin Meyer ⁴



Affiliations

• PMID: 41501066
• DOI: 10.1038/s41467-025-68137-x

Free article Abstract

Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic. Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States. These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies. In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodies. Additionally, we find that AS03-adjuvanted pandemic H1N1 vaccination increases H5N1 cross-reactive antibodies significantly in a pandemic H1N1 immunologically partially naïve population. Furthermore, we show that immune imprinting causes distinct H5N1 cross-reactive antibody patterns pre-vaccination.

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Strengthening our immunity against the risk of avian flu

Published on February 10, 2026

A team from the University of Geneva (UNIGE) has shown that certain antibodies against seasonal flu also target avian flu. Stimulating these antibodies would strengthen our protection in the event of a pandemic.

Are seasonal flu antibodies also effective against avian flu? A team from the University of Geneva (UNIGE) has shown that a specific type of antibody linked to the former virus, and already present in the general population, could provide basic protection against the latter. This protection, however, varies according to age and vaccination history. Published in Nature Communications , these results provide key insights for anticipating a potential avian flu pandemic.

Circulating in many parts of the world – including Switzerland – the avian influenza A H5N1 virus spreads primarily among birds. However, several transmissions to cattle, and subsequently to humans, have recently been observed in North America ( 71 cases reported in the United States), reviving concerns about the risk of a future pandemic. A variant from a specific evolutionary lineage of the virus – clade 2.3.4.4b – is attracting particular attention from epidemiologists due to its virulence.

Several studies have shown that pre-existing immunity against human seasonal influenza viruses could modulate the severity of an H5N1 infection. "We have all been exposed to these viruses and therefore possess antibodies directed against them, which share a common genetic basis with H5N1. Some of these antibodies – known as cross-reactive antibodies – are thus able to recognize H5N1 and, to some extent, fight it," explains Benjamin Meyer, a scientific collaborator at the Vaccinology Center of the Department of Pathology and Immunology at the Faculty of Medicine of the University of Geneva.

"People vaccinated in 2009 during the H1N1 flu pandemic now have higher concentrations of cross-reactive antibodies."

Vaccinated in 2009? More antibodies.
Thanks to recent research, Benjamin Meyer and his team have shown that these cross-reactive antibodies primarily target the virus's "stem," which it shares with seasonal flu, and not its "head," which changes frequently. But most importantly, the scientists discovered that these antibodies, unlike others, do not prevent the H5N1 virus from entering cells, but rather block its ability to spread from one cell to another. Indeed, once replicated within its host, the virus detaches but remains attached to the cell membrane. To break free and continue its infection, it uses a protein that acts like molecular scissors. It is this "cutting" process that the cross-reactive antibodies inhibit, with varying degrees of effectiveness depending on the individual.

By examining these individual differences, scientists highlighted another important finding: people vaccinated in 2009 during the H1N1 influenza pandemic—with a vaccine containing an adjuvant designed to amplify the immune response—now have higher concentrations of cross-reactive antibodies capable of effectively neutralizing the H5N1 virus. In people who received a standard seasonal flu vaccine, no increase in cross-reactive antibodies was detected. This enhanced immune response could be associated with less severe symptoms in the event of avian influenza infection.

Year of birth also important
“Our study also shows that early exposure during life plays an important role: people born before 1965 — who were exposed during childhood to seasonal flu viruses of subtypes H1 or H2 — naturally have higher levels of antibodies against H5N1. Conversely, those born later were exposed to other subtypes of seasonal flu and have a lower level of baseline protection,” says Mariana Alcocer Bonifaz, researcher at the Vaccinology Centre of the Department of Pathology and Immunology of the Faculty of Medicine of UNIGE, and first author of this publication.

These results highlight the importance of adjuvanted seasonal influenza vaccination for broadening the immune response to the risk of an avian influenza pandemic. Such a strategy would also offer a major advantage in the event of a pandemic: the amount of H5N1 vaccine—already available—required per person would be significantly lower compared to influenza vaccination without adjuvant, thereby increasing overall vaccination capacity for the same level of production. This work was supported by an Ambizione grant from the Swiss National Science Foundation (SNSF).

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Contact
Benjamin Meyer,
Scientific Collaborator,
Center for Vaccinology,
Department of Pathology and Immunology,
Faculty of Medicine,
University of Geneva,
+41 22 379 57 80,
Benjamin.Meyer@unige.ch

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This research is published in
Nature Communications
DOI: 10.1038/s41467-025-68137-x

https://www.unige.ch/medias/2026/ren...grippe-aviaire