Nasal spray could protect against any strain of flu and the method could work against other pathogens

[University of St Andrews] Scots scientists have developed a novel treatment that could protect against any strain of the flu.

It is hoped that the new development, led by researchers at the University of St Andrews, has the potential to guard against current, future and even pandemic strains of the virus.

In an international effort, the scientists involved say that the preventative treatment could be used as a ‘frontline defence’ before an effective flu vaccine is developed. Leading influenza experts say the new development is ‘very exciting and potentially of great importance in this era’.

PNAS – Prevention of influenza by targeting host receptors using engineered proteins

Researchers have developed a new class of host-targeted biologics to prevent influenza by engineering multivalent carbohydrate-binding modules that bind with high affinity to sialic acid, the critical component of the influenza virus cell surface receptor. Mouse studies reveal a remarkable efficacy: a single 1-μg dose of the lead biologic given 7 d before a lethal challenge with 2009 pandemic H1N1 influenza virus provides complete protection. This new approach has the potential to be a front-line defense against any current and future influenza virus, overcoming viral escape to vaccines and antivirals. In addition, the biologics may have broader application against other respiratory pathogens.

Strands of engineered proteins bind to a mouse’s cells to ward off flu viruses. University of St. Andrews

Abstract

There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. We show that multivalent biologics, engineered using carbohydrate-binding modules specific for sialic acid, mask the cell-surface receptor recognized by the influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1 influenza virus. The most promising biologic protects mice when given as a single 1-μg intranasal dose 7 d in advance of viral challenge. There also is sufficient virus replication to establish an immune response, potentially protecting the animal from future exposure to the virus. Furthermore, the biologics appear to stimulate inflammatory mediators, and this stimulation may contribute to their protective ability. Our results suggest that this host-targeted approach could provide a front-line prophylactic that has the potential to protect against any current and future influenza virus and possibly against other respiratory pathogens that use sialic acid as a receptor.

More on the research

The BBSRC and MRC-funded research was led by Professor Garry Taylor and Dr Helen Connaris in the Biomedical Sciences Research Complex at St Andrews. They said “We have developed an alternative host-targeted approach to prevent influenza by synthesising novel proteins, or biologics, that are designed to mask specific sugar molecules that line the respiratory tract.

“The influenza virus, and indeed other respiratory pathogens, needs to bind to these sugars to gain entry to our cells to start the infection process.”

The novel method was tested in mice by collaborators at the Roslin Institute in Edinburgh and at St Jude Children’s Research Hospital in Memphis. These studies showed that a single intranasal dose completely protects mice even when given 7 days before a lethal challenge with the pandemic 2009 H1N1 virus. As well as surviving, the mice develop antibodies against the virus suggesting that they are “vaccinated” against any future exposure to the virus.

One of the authors of the study, Dr Robert Webster, Rose Marie Thomas Chair of Virology at St Jude, is one of the world’s foremost experts on influenza. He said, “The work is very exciting and potentially of great importance in this era of emerging viruses like H7N9 that have pandemic potential.”

Influenza remains a constant worldwide health threat with annual epidemics claiming up to 500,000 lives each year according to the World Health Organisation. The emergence of new strains from birds in recent years has revealed the remarkable ability of the virus to cross species barriers and to pose pandemic health threats.

While vaccines are the cornerstone of prevention, these are not always effective and take time to develop in quantities needed to treat whole populations. Antivirals are available, but the very recent Cochran report has highlighted the limited effectiveness of Tamiflu despite the UK government having spent almost £0.5 billion on stockpiling the drug.

Dr Connaris, a Senior Research Fellow at the University of St Andrews, said, “We anticipate our novel preventative approach being used as a frontline defense against new pandemic strains before an effective vaccine is developed, but the approach could also be used routinely against seasonal strains to protect health and care workers.”

Professor Taylor, Professor of Molecular Biophysics at St Andrews, added, “The recent Cochran study revealing the limited effectiveness of Tamiflu which has been stockpiled by several governments at vast expense shows how new approaches are required.

“We believe that our approach has the potential to be used as a preventative against any current and new virus that emerges, such as H5N1, H7N9 and the very recent H10N8. Given that several other respiratory pathogens use the same entry route for infection, then our approach has a potentially broader application.”

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