19 April 2023
New research from the Malaghan Institute has identified that MAIT-cells, a type of immune cell found in mucosal tissues, are a promising target for future vaccines, with the potential to create stronger, more protective immune responses against pathogens at the site of infection.
Many infectious agents, including those that cause the flu and Covid-19, typically gain access to our body through similar pathways, most commonly through the nose or mouth. In response, our bodies have evolved strategies to help prevent unwanted organisms gaining internal access through these entry points. One way is to line these entryways with viscous, sticky fluid to trap unwanted organisms and hold them in place to then get mopped up by the immune system. These sticky mucus layers are found in many different sites around the body, not just the nose but in the lungs and intestines as well.
Because of their proximity to incoming infections, the immune cells located in and around the mucosa are the cells we most want to train to identify and remove harmful organisms – through vaccination – yet our current vaccines don’t prioritise these cells.
The Malaghan Institute’s vaccine evaluation team, led by Dr Lisa Connor, have plans to change that. They’ve spent several years developing and testing a new form of vaccine, one that is administered to, and specifically targets, the upper airways (nose and lungs) and the immune cells living there. What’s more, rather than an injection, these vaccines could be delivered via nasal spray.
“Mucosal vaccines are vaccines that are administered into the mucosal tract, such as the respiratory or digestive system,” says Kaitlin Buick, a PhD student at the Malaghan Institute and Te Herenga Waka – Victoria University of Wellington and co-author of the paper. “For example, a vaccine that is inhaled or swallowed instead of the typical needle injection. Mucosal immune responses can provide additional defence against respiratory viruses, including influenza and Covid-19.”
The immune cells that live in the mucosa have uniquely adapted to deal with oncoming threats. These specialised immune cells make perfect targets for vaccines, as these are the cells that are best positioned in the body to recognise and quickly respond to an infection. Additionally, antibody-producing immune cells in the mucosal tissue secrete a type of antibody called IgA that has the job of neutralising harmful pathogens in the mucosal surfaces of the body, which helps prevent infections. However, traditionally vaccines are administered intramuscularly – an injection into the arm. As such, they do not typically activate an immune response in the mucosa, and therefore do not provide the same level of protection against infections that target mucosal surfaces.
Developing mucosal vaccines has presented multiple challenges. The vaccine needs to overcome the physical barriers of the mucosa, such as the mucus layer, but also needs to be safe to prevent damage to the delicate lung structure.
“The aim of giving a mucosal vaccine is to build up a strong immune response against the pathogen throughout the body, but importantly, at the locations in the body where pathogens can invade. Vaccines injected into the arm give strong immune responses that circulate around the body but can be limited in generating protective immune responses in those more vulnerable mucosal sites, thus giving the pathogen slightly more time and opportunity to infect us.”
Published in Cell Reports, the team’s research showed that MAIT-cells, a type of mucosal-associated immune cell, makes a promising target for mucosal vaccines.
“We included an ingredient in our vaccine that targets and activates a specific immune cell in the lung called a MAIT-cell. When this ingredient was given through the nose along with parts of SARS-CoV-2 or influenza viruses, it activated the mucosal immune system by helping other immune cells do their job better without causing excessive inflammation and damage.
“The results suggest that MAIT cells could be a promising target for mucosal vaccines that can protect against respiratory infections like COIVD-19 and influenza,” says Kaitlin.
“There continues to be growing research into mucosal vaccines due to their potential benefits and there are current preclinical and clinical trials ongoing, some of which include mucosal vaccines for SARS-CoV-2. So while there is work yet to be done, there are positive steps forward to develop mucosal subunit vaccines.”
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