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Article

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

1
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
2
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA
3
Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea
4
Department of Parasitology, Inje University College of Medicine, Busan 47392, Republic of Korea
5
Department of Infectious Disease and Malaria, Paik Institute of Clinical Research, Inje University, Busan 47392, Republic of Korea
6
Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, 02447, Republic of Korea
7
Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2025, 13(6), 600; https://doi.org/10.3390/vaccines13060600
Submission received: 2 May 2025 / Revised: 23 May 2025 / Accepted: 30 May 2025 / Published: 31 May 2025
(This article belongs to the Special Issue Virus Pandemics and Vaccinations)

Abstract

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. Conclusion: 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.
Keywords: orally dissolving film; vaccine; influenza virus; mucosal immunity orally dissolving film; vaccine; influenza virus; mucosal immunity

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MDPI and ACS Style

Yoon, K.-W.; Mao, J.; Eom, G.-D.; Heo, S.I.; Chu, K.B.; Lee, M.S.; Quan, F.-S. Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus. Vaccines 2025, 13, 600. https://doi.org/10.3390/vaccines13060600

AMA Style

Yoon K-W, Mao J, Eom G-D, Heo SI, Chu KB, Lee MS, Quan F-S. Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus. Vaccines. 2025; 13(6):600. https://doi.org/10.3390/vaccines13060600

Chicago/Turabian Style

Yoon, Keon-Woong, Jie Mao, Gi-Deok Eom, Su In Heo, Ki Back Chu, Mi Suk Lee, and Fu-Shi Quan. 2025. "Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus" Vaccines 13, no. 6: 600. https://doi.org/10.3390/vaccines13060600

APA Style

Yoon, K.-W., Mao, J., Eom, G.-D., Heo, S. I., Chu, K. B., Lee, M. S., & Quan, F.-S. (2025). Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus. Vaccines, 13(6), 600. https://doi.org/10.3390/vaccines13060600

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