Deadly respiratory viruses, like those causing COVID-19 and flu, spread among people through a simple act: breathing. With each inhalation, these airborne pathogens enter the body through our noses, throat and lungs, and replicate in the infected person before being transmitted to another unsuspecting victim.
For COVID-19, this led to the rapid spread of the devastating virus around the world. The raging pandemic resulted in hundreds of millions of infections and over 20 million deaths, alongside prolonged lockdowns and severe disruption to our health systems and economies.
To tackle the immense devastation, a stream of successful COVID-19 vaccines were created and rolled out around the world at record scale and speed.
“Offering strong protection against severe disease and death, these vaccines were vital to bringing an end to the pandemic” explains Christine Dahlke, CEPI’s Senior Translational Immunology Lead. "However, despite their success, they did not prevent infection, stop illness, or avert the long-term effects of COVID‑19." As a result, SARS‑CoV‑2—the virus responsible for COVID‑19—continued to circulate even during global vaccination efforts.
A growing body of researchers and funders, including CEPI, are now looking at whether we can design vaccines that not only protect against illness but stop viral infection, and therefore transmission, entirely. To do so, they want to look at inducing a specific form of immune response known as mucosal immunity which targets the specialised immune cells that line our nose, throat and lungs.
On the nose
Our smelling organs contain mucosal passages lined with immune cells capable of producing antibodies, like IgA, that neutralise viruses in the mucus before they infect cells. Similarly, other tissues in the lungs and gut also contain armies of these specialised mucosal immune defences, providing a powerful frontline barrier at the point at which viruses first enter the body. These tissues therefore operate as a gateway for infection but also a potential site for intervention.
Although current COVID-19 vaccines elicit strong whole-body immune responses, there is limited evidence showing that they induce mucosal immunity. But vaccines administered directly to target these entry points, for example through inhalers or nasal sprays, could be a gamechanger.
If the virus cannot replicate in the nose or throat, infected individuals would shed fewer viral particles, making onward transmission far less likely. By blocking transmission at its source, these vaccines could be crucial to CEPI’s ambition to rapidly contain outbreaks before they spread to pandemic proportions.
Enter MUSICC
To better understand how mucosal immunity works and uncover whether we can design coronavirus vaccines targetting these entry points, CEPI with support from the European Commission, has invested up to $57 million in a global consortium of scientists. Led by the UK’s Imperial College London, the MUSICC research programme will assess whether such vaccines could stop infection and onward transmission exactly where the viruses first strike.
As part of the research, volunteers will take part in human challenge studies, where they are safely infected with a coronavirus in a controlled laboratory setting to give scientists detailed insights into what happens during the earliest moments of infection.
“The way in which we protect ourselves from viral threats could be right under our noses (and in our mouths and lungs)” explains Dahlke. “If we can strengthen immunity at these entry points, we can stop infections before they start - and dramatically limit transmission and the epidemic curve in the process.”
MUSICC will also look at whether strengthening mucosal immune responses could help slow the emergence of new variants by reducing opportunities for viruses to replicate and mutate in new hosts.
Transforming epidemics and pandemics
Over the next few years, MUSICC will conduct a series of experiments to advance tools to better understand the mucosal immune response and uncover how mucosal-targetting vaccines work.
The challenge is immense. Researchers first need to uncover the mechanics behind mucosal immunity, work out how long mucosal immune response can last and unpack what vaccine technology designs could offer this type of protection. But, if successful, targeting immunity at viral points of entry, like the nose – once overlooked in viral research - could fundamentally reshape our pandemic readiness.
This shift from protecting severe disease to stopping transmission altogether represents one of the most promising frontiers in modern vaccinology and our work to prepare for future global threats.
Read more about mucosal immunity and the MUSICC programme in this article on the MUSICC website.
Image Credit: Imperial College London
Ronald Kakeeto: My Fellowship at CEPI
Dr Navneet Bichha: My Fellowship at CEPI
