Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus.

Background

Self-administered orally dissolving films (ODFs) encapsulating inactivated influenza vaccines represent an effective strategy for stimulating mucosal immunity. While this vaccination method offers several advantages over conventional influenza vaccines, a comparative efficacy study remains lacking.

Methods

Female BALB/c mice were immunized with inactivated A/PR/8/34 (H1N1) either via orogastric inoculation or through the oral mucosal delivery using pullulan and trehalose-based ODF vaccines. Each group received equivalent antigen doses across three immunizations. Humoral responses and antibody functionality were assessed using sera collected post-immunization. After lethal viral challenge, other immunological and virological parameters were determined in corresponding tissues. Body weight and survival were monitored over a 14-day period after challenge.

Results

ODF vaccination elicited significantly higher virus-specific IgA levels, HAI titers, and neutralizing antibody activity than oral gavage. After the viral challenge, ODF-immunized mice exhibited stronger IgG and IgA responses in respiratory tissues, increased antibody-secreting cells in lungs and spleen, and elevated germinal center B cells and CD8+ T cell responses. Both vaccination methods reduced lung pro-inflammatory cytokines and provided full protection against lethal challenge; however, the ODF group showed lower cytokine levels, better weight maintenance, and reduced viral loads.

Conclusions

ODF vaccination elicits more robust systemic and mucosal immune responses than oral vaccination and may serve as a promising alternative method of influenza vaccine delivery.