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 COVID-19 pandemic has left an indelible mark on human history, underscoring the urgent need for effective strategies against future pandemics. The World Health Organization (WHO) and many nations have already begun preparations to address potential pandemics caused by “Disease X.” One such threat is the H5N1 avian influenza virus, which has been detected in humans since 1997 and has spread globally, causing cross-species infections.

Researchers at the State Key Laboratory for Emerging Infectious Diseases at the University of Hong Kong (HKU) and the InnoHK Centre for Virology, Vaccinology and Therapeutics (CVVT) have pioneered an influenza virus vector-based nasal spray vaccine platform. This innovative approach has been used to develop a nasal spray H5N1 avian influenza vaccine, offering a critical reserve against future outbreaks.

The COVID-19 pandemic highlighted the importance of rapid vaccine development and deployment. Current vaccines, including mRNA vaccines, effectively prevent severe disease and reduce mortality but fail to curb viral transmission. A nasal spray vaccine offering single-dose protection could play a pivotal role in outbreak control by rapidly inducing mucosal immunity at the primary site of viral entry.

The HKU and CVVT team’s research has shown that their nasal spray H5N1 avian influenza vaccine has a high safety profile and is able to induce comprehensive immunity, including neutralising antibodies, T-cell responses, and mucosal immunity in the upper respiratory tract. Crucially, a single dose provides robust protection against infection and sustains immune memory.

Further clinical trials could position this vaccine as a critical reserve for future H5N1 outbreaks, drastically shortening deployment timelines. Its nasal delivery mechanism also promises to curb viral transmission early in an outbreak. This research was funded by the InnoHK initiative of the Innovation and Technology Commission of Hong Kong Special Administrative Region Government, with key contributors including Professor Chen Honglin, Dr Wang Pui, Dr. Deng Shaofeng, Ph.D. candidate Liu Ying, and Professor Yuen Kwok Yung, Professor To Kai Wang Kelvin from the Centre for Virology, Vaccinology and Therapeutics, State Key Laboratory for Emerging Infectious Diseases and the Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine.