Photo credit: CDC
Five flu pandemics have occurred since 1900. In a typical year, 5–15% of the population contracs influenza. Whilst it can infect people of all ages but it tends to disproportionately cause severe illness in the elderly, the very young, and those who have chronic health issues. Influenza viruses, particularly IAV, evolve quickly, so flu vaccines are updated regularly to match which influenza strains are circulating. Historically, the influenza A virus is responsible for human pandemics derived from groups 1 (H1N1 and H2N2) and group 2 (H3N2), however, influenza vaccines are only effective if there is an antigenic match between the vaccine and circulating strains.
Influenza viruses spread through respiratory droplets produced by coughing and sneezing, through aerosols and contaminated surfaces. Therefore, vaccines are required which can protect against both infection and transmission of viruses.
Seasonal flu vaccines are not always protective; mismatches between seasonal flu vaccine strains and circulating viruses frequently occur. There is an urgent need for a new vaccine without annual formulation.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the 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.
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. 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 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.
Photo credit: CDC