Researchers from the University of Maryland shared in November 2023 that they have made progress in developing a nasal spray vaccine that delivers the SARS-CoV-2 spike protein to cells in the airway. Their research paper, published in Nature communications, reveals that in animal studies this has shown a significant reduction in infection and spread of COVID-19. The team believes that their technology has applications in other respiratory illnesses, such as influenza and RSV. 

Target the source 

The paper states that SARS-CoV-2 can be shed from asymptomatic infections and spreads “predominantly through droplets and airborne aerosols”. Because the virus “first enters the nose or mouth” and then replicates within the epithelial cells of the nasopharynx, prompting an upper respiratory infection, the nasal mucosa and nasopharynx are the “primary sites of exposure” to the disease before dissemination to other areas.  

Current intramuscular vaccines “can effectively prevent severe diseases and deaths”, but do not effectively “elicit protective mucosal immunity in the upper respiratory tract”. Therefore, “opportunistic breakthrough infections” are enabled in vaccinated individuals. Additionally, SARS-CoV-2 can “linger in the nasal mucosa” even after infection has been cleared. The authors suggest that evolutions to the virus necessitate a “safe and protective mucosal vaccine” to “block the viral entry and reduce or eliminate the viral spread”.  

The ideal solution would be nasal spray vaccines, which can “elicit local secretory IgA antibodies and resident T and B cell responses in the upper respiratory tract and the lungs”. Furthermore, they are less invasive, with potential to increase vaccine uptake. In their research, the Maryland team determined the ability of a protein called neonatal Fc receptor (FcRn) to deliver an intranasally-administered antigen and induce protective mucosal and systemic immunity to SARS-CoV-2 infection.  

Progress in animals 

The team administered their vaccine to mice before exposing them to ancient SARS-CoV-2, Delta, and Omicron variants of COVID-19. The mice that were exposed to the Delta variant died, while between 83% and 100% of vaccinated mice survived.  

Furthermore, although mice exposed to major Omicron variants survived, there was a significant reduction in inflammation and virus loads in vaccinated mice compared with unvaccinated mice. Another result that comparisons between nasal and injected vaccination revealed a more potent immune response in the airway and lungs for the nasal vaccine.  

The results indicate a positive future for FcRn-mediated respiratory immunisation. The study authors describe it as an “effective and safe” strategy to maximise the “efficacy of vaccinations against infection and transmission”. 

How do you think nasal spray vaccination could improve our efforts against SARS-CoV-2? Would you be more inclined to receive or administer this technology? 

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