Check out our paper in @ImmunityCP! I think it’s pretty neat, read more in the thread below: Mucosal plasma cells are required to protect the upper airway and brain from infection cell.com/immunity/fullt…
The highlights:
-Blood antibody can’t protect the entire nose from infection
-Discovery of the blood-olfactory barrier (BOB!)
-Mucosal plasma cells home to the nose to provide protection
-Only some vaccine adjuvants make these plasma cells
-Blood antibody can’t protect the entire nose from infection
-Discovery of the blood-olfactory barrier (BOB!)
-Mucosal plasma cells home to the nose to provide protection
-Only some vaccine adjuvants make these plasma cells
For respiratory diseases like #COVID, #vaccines give us great protection from severe disease in the lung. But do they protect the upper respiratory tract? Mild nasal infection seems common even with high levels of blood antibody, allowing for continued transmission of disease.
Do we need tissue-specific immune responses to protect the nasal passages? Or is systemic antibody generation sufficient for protection? We found that blood-borne antibodies cannot protect against viruses that infect the olfactory tissue in the nose.
Blood antibodies can protect the respiratory epithelium in the nose, but not the olfactory epithelium. Why is this important? Viral replication in the olfactory tissue might allow for more “breakthrough” infections and continued disease spread.
But the olfactory epithelium is special because it contains our body’s smell-sensing cells. These cells form a direct pathway into the brain to relay scents. Great for smelling roses, but bad because neuroinvasive pathogens can hijack this route to get into the brain!
So if blood antibodies can’t protect olfactory tissue, our brain is left exposed to these nasty diseases! So why can’t antibodies protect this really important mucosal tissue? We discovered that a blood-olfactory barrier exists, which we’ve named the BOB.
The BOB potentially acts similarly to the blood-brain barrier, keeping bad stuff in our blood from entering the brain. So how do we protect the nose and the brain from getting infected? We found that previous infection could make mice completely immune at the olfactory surface.
This happens because mucosal plasma cells are programmed to enter the olfactory mucosa and secrete locally protective antibody. By residing in the tissue, they can supply antibodies directly to the mucosal surface.
What signals tell plasma cells to go to the olfactory mucosa? We found that T cell help and Cxcr3 signaling in the lymph node are important for this plasma cell differentiation. We wanted to see if vaccines could provide these signals to plasma cells, or if only infection could.
Conventional vaccine adjuvants, like alum, were incapable of telling plasma cells to migrate into the olfactory tissue. But we did find that certain adjuvants, like the mucosal adjuvant dmLT, were able to generate olfactory plasma cells and provide complete protection!
More important than the route of the vaccine, per say, is the type of adjuvant signaling the B cells receive. So intranasal approaches may work, but in theory an intramuscular vaccine could drive this same type of protection!
More important than the route of the vaccine, per say, is the type of adjuvant signaling the B cells receive. So intranasal approaches may work, but in theory an intramuscular vaccine could drive this same type of protection!
We also tested whether the Pfizer-BioNTech vaccine could protect the olfactory surface, and we found that it may be able to drive tissue-specific protective effects in a mouse model of COVID infection.
We also tested whether the Pfizer-BioNTech vaccine could protect the olfactory surface, and we found that it may be able to drive tissue-specific protective effects in a mouse model of COVID infection.
The takeaways:
-Circulating antibody alone can’t protect the URT
-The olfactory mucosa is compartmentalized by the blood-olfactory barrier (BOB)
-The upper airway and brain can be protected by mucosal plasma cells
-Only some vaccine adjuvants can generate olfactory plasma cells
-Circulating antibody alone can’t protect the URT
-The olfactory mucosa is compartmentalized by the blood-olfactory barrier (BOB)
-The upper airway and brain can be protected by mucosal plasma cells
-Only some vaccine adjuvants can generate olfactory plasma cells
Disclaimer: all of these studies were done with mice, and we still need to see if this biology is mirrored in humans! We did find that plasma cells can be detected in human olfactory tissue, so it seems plausible
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