Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. The virus is extremely infectious, resulting in rapid worldwide circulation. The virus mutates constantly, resulting in more infectious variants like Alpha, Beta, Gamma, Delta and Omicron and variants that manage to evade immunity of the vaccinated population like the recently described BA.5 variant. The spikes on the surface of SARS-CoV-2 contain the receptor-binding domains that recognize and bind to ACE2 receptors present on epithelial cells, allowing the virus to enter. So, SARS-CoV-2 replication usually starts in epithelial cells lining the oral and nasal cavities, initiating an upper respiratory tract infection before disseminating to the lungs and other tissues/organs.

SARS-CoV-2 is highly communicable through the respiratory system, as a result of viral spread predominantly through droplets and airborne aerosols but also through viral shedding from individuals with asymptomatic infections. The currently authorized intramuscular SARS-CoV-2 vaccines are effective in preventing severe disease and death by COVID-19. However, they are designed to elicit systemic immunity but not protective mucosal immunity in the upper respiratory compartment. It is not surprising that low level of viruses or viral RNA are frequently detected in nasal swabs and breakthrough cases in fully vaccinated individuals have been reported. In other words, SARS-CoV-2 virus can linger in the nasal mucosa and upper respiratory system even after the infection in the lungs was cleared in vaccinated individuals. The lack of protective immunity in the upper respiratory mucosa certainly allows for opportunistic breakthrough infections in vaccinated recipients. The emergence and rapid spread of the SARS-CoV-2 variants, especially the Omicron variant, exacerbate the situation. The ongoing evolution of SARS-CoV-2 necessitates a different and more effective vaccination strategy. Our dual mode-of-action vaccine addresses the urgent need to eliminate the viral load from the upper respiratory system while at the same time inducing systemic immunity.