Hydroxypropyl Cellulose Enhances Immune Responses to the Current Seasonal Influenza Vaccine in Mice

Influenza A and B viruses cause annual epidemics and continue to pose global public health concerns. The most effective approach to preventing or mitigating the severity of influenza is vaccination. Inactivated split influenza HA vaccines are commonly used worldwide due to their strong safety profile and broad range of target groups; however, their efficacy is suboptimal, especially in the elderly. Adjuvants are used to enhance the effectiveness of some influenza vaccines, but few adjuvants have been approved for human vaccines. Previously, we identified hydroxypropyl cellulose as a promising adjuvant for the split influenza HA vaccine for the 2015-2016 and 2016-2017 influenza seasons. Here, we evaluated whether hydroxypropyl cellulose could enhance the efficacy of the quadrivalent split HA vaccine for the 2023-2024 influenza season, which contains the HA proteins of A/Victoria/4897/2022 (H1N1)pdm09 and three other strains. Using a mouse model, we performed immunogenicity studies and assessed protective efficacy against challenges with homologous and heterologous H1N1pdm09 virus strains. We found that hydroxypropyl cellulose in combination with the HA vaccine generated higher virus-specific IgG antibody titers compared to the vaccine alone. The adjuvanted vaccine provided complete protection against homologous challenge and enhanced viral clearance from respiratory organs. Notably, the adjuvanted vaccine demonstrated cross-protective efficacy against heterologous H1N1pdm09 virus challenge, improving survival rates compared to vaccine alone. Our results demonstrate that hydroxypropyl cellulose has potential as an adjuvant for current seasonal influenza vaccines.