Newly discovered barrier prevents immunity from reaching smell-sensing cells: The structure, dubbed the BOB, fits with some of the mysteries of COVID

Duke scientists have identified a previously unknown barrier that separates the bloodstream from smelling cells in the upper airway of mice, likely as a way to protect the brain.

But this barrier also ends up keeping some of the larger molecules of the body’s immune system out, and that may be hindering the effectiveness of vaccines.

It makes sense to have a protective barrier for the olfactory cells lining the nose, because they offer a direct path to the olfactory bulb of the brain, making them effectively extensions of the brain itself, said lead researcher Ashley Moseman, an assistant professor of immunology in the Duke School of Medicine.

However, the new barrier, which his team has dubbed the BOB — the blood-olfactory barrier — also might be keeping vaccines against respiratory viruses from being more effective by preventing those antibodies from reaching the mucous on the surface of the nose, the first barrier a virus encounters.

The team was trying to understand better how the immune system protects the upper respiratory tract by infecting mice with a virus called vesicular stomatitis virus, or VSV, that is known to penetrate to the central nervous system. Once inhaled, VSV readily infects the olfactory sensing cells and rapidly replicates, reaching the olfactory bulb of the brain within a day. Although it can lead to paralysis and death, it is usually cleared by a T cell response.

“VSV is excellent at infecting olfactory sensory neurons, and when it can do that, it will get into the brain,” Moseman said. “Even if you have antibodies in circulation, the blood-olfactory barrier prevents these antibodies from reaching the airway surface, and VSV will get into the brain.”

They wanted to understand better how a prior infection could provide protection against subsequent infection. What they found was that while the BOB prevented circulating antibody protection, it does allow antibody secreting plasma cells to enter olfactory tissues and locally produce neutralizing antibodies. The findings appear Sept. 21 in the journal Immunity.

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