The threat of future pandemics has been heightened by the emergence of new influenza viruses. In recent years, researchers from the Helmholtz Centre for Infection Research (HZI) and the Medical Center — University of Freiburg have made significant progress in understanding how these viruses interact with host cells.

Led by Professor Christian Sieben’s team at HZI, scientists have developed a novel method to study the initial contact between influenza viruses and host cells. This breakthrough allows researchers to investigate the complex process of viral entry in unprecedented detail.

The researchers immobilized individual viruses on microscopy glass surfaces and then seeded cells on top. This innovative “upside-down” experimental setup enables scientists to analyze the critical moment when viruses interact with cells but do not enter them, stabilizing the initial cell contact for further investigation.

Using high-resolution and super-resolution microscopy, the team demonstrated that contact between the virus and the cell surface triggers a cascade of cellular reactions. The accumulation of local receptors at the binding site, the recruitment of specific proteins, and the dynamic reorganization of the actin cytoskeleton are just some of the processes observed in this study.

What’s more remarkable is that researchers applied their method not only to an established influenza A model but also to a novel strain found in bats. The H18N11 virus, which targets MHC class II complexes rather than glycans on the cell surface, was shown to cluster specific MHCII molecules upon contact with the cell.

This groundbreaking research has significant implications for understanding alternative receptors used by new and emerging influenza viruses. The findings provide a critical basis for investigating potential pandemic pathogens in a more targeted manner, identifying new targets for antiviral therapies, and ultimately developing effective treatments against future pandemics.

The EU project COMBINE, launched in 2025 and coordinated by Professor Sieben’s team at HZI, aims to investigate the virus entry process of newly emerging viruses. This research has far-reaching implications for understanding and combating infectious diseases, making it a significant contribution to the global fight against pandemics.

“The world is witnessing a breakthrough in influenza management with the discovery that a single oral dose of baloxavir marboxil (baloxavir) can significantly reduce the transmission of influenza within households. This landmark study, published in The New England Journal of Medicine, sheds light on the first robust evidence that an antiviral treatment can curb the spread of influenza to close contacts.

Conducted by a team of international researchers including the LKS Faculty of Medicine at the University of Hong Kong (HKUMed), the CENTERSTONE trial enrolled 1,457 influenza-positive index patients and 2,681 household contacts across 15 countries from 2019 to 2024. The participants were randomly assigned to receive either baloxavir or a placebo within 48 hours of symptom onset.

The primary endpoint was laboratory-confirmed influenza transmission to household contacts by day 5. And the results are nothing short of remarkable.

‘These findings highlight baloxavir’s potential not only to treat influenza but also to reduce its spread within communities,’ said Professor Benjamin Cowling, co-author of the study and Helen and Francis Zimmern Professor in Population Health. ‘This dual effect could transform how we manage seasonal influenza and prepare for future pandemics.’

The study underscores the complementary role of antiviral drugs alongside vaccination, particularly in unvaccinated populations or during pandemics when vaccines may not be immediately available. The discovery opens doors to new possibilities in public health, where a single dose of baloxavir could become an essential tool in managing and containing outbreaks.

This groundbreaking research has far-reaching implications for the way we approach influenza management and pandemic preparedness. It’s a testament to human innovation and our unwavering commitment to protecting global health.”

The study of rotavirus has taken a significant leap forward with the discovery that the whole rotavirus genome – not just its two surface proteins – affects how well vaccines work. Researchers have found that genetic differences between circulating rotavirus strains and vaccine strains may impact vaccine effectiveness, leading to a better understanding of why some strains are more likely to infect vaccinated individuals.

The study, published in eLife, used a novel approach to estimate rotavirus vaccine effectiveness by analyzing the full genetic code of each virus strain. The researchers found that individuals vaccinated with Rotarix (RV1) were more likely to be infected by rotavirus strains that were significantly genetically different from the vaccine – over 9.6% different in their full genome.

The study revealed that circulating viral strains that were genetically similar to the vaccine had a viral backbone called genogroup 1 (Wa-like), while those that were genetically distant tended to have a different viral backbone called genogroup 2 (DS-1-like) or had mix-and-match variants known as reassortant strains.

Vaccine effectiveness results also reflected this genetic pattern, with the Rotarix (RV1) vaccine providing strong protection against genetically similar viral strains but its protection dropping significantly for more genetically distant strains. The RotaTeq (RV5) vaccine followed a similar pattern, but differences in its effectiveness were less pronounced.

The researchers found that vaccination patterns in different locations influenced the rotavirus strains circulating in the population. They discovered that in places where more people used Rotarix (RV1), rotavirus strains that were genetically distant dominated. This suggests that over time, rotavirus is naturally adapting in response to vaccine-induced immunity, leading to shifts in the genetic makeup of circulating strains to favor those genetically different from the vaccine.

The study highlights the need to continually monitor viral evolution to maintain vaccine effectiveness in the long term. The researchers caution that their study is limited by a relatively small sample size of cases and call for future studies to further validate their findings in other settings where whole genome sequencing data is more widely available.

The team’s framework for using whole genome sequencing data to understand how all gene segments contribute to immune protection could be crucial for maintaining the long-term success of rotavirus vaccines. This study shows that looking at the entire genetic structure of rotavirus gives a much clearer picture of how well vaccines work compared to just looking at the two surface proteins, and highlights the importance of incorporating the full genomic structure of viruses when designing vaccines.