The nose knows: new research explores next generation of nasal vaccines

“Your nose has a specialised immune tissue that helps your body stop viruses before they spread,” says postdoctoral researcher Dr Isabelle Montgomerie, who led this research recently published in Mucosal Immunology. 

“In this research we found that a type of immune cell called an NKT-cell that lives in the nasal associated lymphoid tissue gives extra help there, letting the body make stronger antibodies than usual. This finding could be a key in designing better nasal vaccines that stop infections from gaining a foothold in the nose, throat or lung.”

When launching an immune response to a foreign invader, T-cells and B-cells work together to generate protective antibodies specific to the threat they’re facing. Activated B-cells enter germinal centres, a nexus hub of immune cells that create and coordinate antibodies to microscopic threats like viruses and bacteria. 

To efficiently fight a virus or bacteria, we want this process to happen at the site of infection – shortening the window infections have to wreak havoc on our bodies. 

“B-cells internalise foreign proteins and present these proteins to CD4 T-cells as part of the immune response,” says Dr Montgomerie. “Normally, B-cells require CD4 T-cell help to enter germinal centres. However, there are very few CD4 T-cells present in the nasal cavity – which limits the generation of germinal centres in this area.

“However, our research showed that in the nasal-associated lymphoid tissue, where there are very few T-cells, NKT-cells – which are present– can accommodate and step in to help form germinal centres,” she says.

“Even better, these NKT-cells stay active even after repeated stimulation and continue to give B-cells the signals they need to enter germinal centres, where the strongest antibodies are made.” 

Dr Montgomerie, along with other members of the Connor Lab, believe that by directly stimulating NKT-cells in the nasal cavity, we could develop a new class of nasal vaccines that offer not just protective, but sterilising immunity to certain respiratory infections. 

“These findings could help design better nasal vaccines that stop infections at the site of infection, rather than just reducing symptoms.”

The less time an infectious organism spends in the body, the better. If the immune system can successfully boot a virus or bacteria the moment it enters, the less sick we feel and the less likely we are to pass it on to the next person. 

“Sterilising immunity is essential if we want to prevent future pandemics. Being able to prevent a respiratory virus or bacteria from multiplying in the nose or throat means people can’t spread it to others. Achieving sterilising immunity is key for ending outbreaks quickly and preventing the evolution of new variants.”

What’s more, this kind of vaccine would likely be administered in the form of a nasal spray, rather than an injection, localising the protection to where it’s needed.

“NKT-cells are easy to activate and activate very quickly, which makes them great candidates for vaccine design,” says Dr Montgomerie. “We are currently working on adapting RNA vaccines to be delivered intranasally and incorporating NKT-cell agonists – compounds that stimulate NKT-cells.

“While this research is still in its early stages, we’re excited about where it could lead.”