Compelling new preclinical research led by scientists from Yale University has found intranasal vaccination may be much more effective at generating immunity against a number of respiratory viruses compared to more conventional injection-delivered vaccination.
The COVID-19 pandemic has rekindled great interest in delivering vaccines via inhalable nasal spray. Not only is this kind of vaccine delivery system much easier to administer but for several years researchers have hypothesized it to be potentially more effective against infections that initially take hold in the upper respiratory tract.
“The best immune defense happens at the gate, guarding against viruses trying to enter,” explains senior author on the new study, Akiko Iwasaki.
Immunoglobulin A (IgA) antibodies are one of the immune system’s frontline soldiers. These antibodies are primarily secreted by mucosal surfaces in the body, mostly seen in the nose, gut and lungs.
The idea behind a nasal vaccine is that it could directly train mucous membranes in the nose how to target certain airborne pathogens so an immune response can be mounted as soon as a virus enters a human body. This new study promisingly reveals nasal vaccines not only induce effective IgA responses but may promote broad immunity against more than just the single viral strain in a vaccine.
The study reports on a series of mouse experiments comparing the effects of an influenza vaccine delivered intranasally and more traditionally via injection. The researchers exposed the mice to a number of different influenza strains beyond the one the vaccine was designed to target. The findings revealed the animals receiving the nasal vaccine were much better protected from a broad variety of influenza strains compared to the mice receiving injections.
Focusing on IgA responses the researchers discovered not only did the nasal vaccine induce IgA responses in nasal mucous membranes, but significant levels of IgA secretion were detected in the lungs as well.
“When you look inside the lungs of nasal vs. parenteral primed mice 5 weeks later, nasal primed mice contain tons of plasma cells secreting IgA beneath the epithelium, and IgA is bathing the lumen of the lung,” Iwaskai explains on Twitter. “These IgA secreting cells at 5 weeks post prime are mostly tissue-resident cells (meaning they sit within the lung and do not move around).”
When you look inside the lungs of nasal vs. parenteral primed mice 5 weeks later, nasal primed mice contain tons of plasma cells secreting IgA beneath the epithelium, and IgA is bathing the lumen of the lung 😲 (5/) pic.twitter.com/Gm6WGkCyTg
— Prof. Akiko Iwasaki (@VirusesImmunity) December 11, 2021
And most significantly, these nasal and lung IgA responses were not seen in the animals receiving the vaccine by injection. Only intranasal vaccine administration generated this kind of immune response.
Iinfluenza vaccines were used in these current experiments, however, the researchers are now conducting similar tests in animals with COVID-19 vaccines. Iwasaki says the findings do suggest nasal vaccines could be more effective at producing immunity that is broadly protective against many variants of an individual virus.
“These results indicate that nasal vaccines induce IgA and promote better cross-protective immunity against viral variants, and suggest its utility in combating COVID-19 variants of concern,” she adds.
A number of inhalable nasal COVID-19 vaccines are currently in development, and several are already in early human trial stages. But developing effective nasal vaccines has proved challenging, with several research dead-ends over the past decades suggesting the task could be easier said than done.
The new research was published in the journal Science Immunology.
Source: Yale News
