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

<b>Background</b>: 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 e...

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Main Authors: Keon-Woong Yoon, Jie Mao, Gi-Deok Eom, Su In Heo, Ki Back Chu, Mi Suk Lee, Fu-Shi Quan
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/6/600
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author Keon-Woong Yoon
Jie Mao
Gi-Deok Eom
Su In Heo
Ki Back Chu
Mi Suk Lee
Fu-Shi Quan
author_facet Keon-Woong Yoon
Jie Mao
Gi-Deok Eom
Su In Heo
Ki Back Chu
Mi Suk Lee
Fu-Shi Quan
author_sort Keon-Woong Yoon
collection DOAJ
description <b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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<sup>+</sup> 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. <b>Conclusions</b>: 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.
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spelling doaj-art-246b9e4c4d4a4744a1f6b1ea3ef875802025-08-20T03:26:52ZengMDPI AGVaccines2076-393X2025-05-0113660010.3390/vaccines13060600Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza VirusKeon-Woong Yoon0Jie Mao1Gi-Deok Eom2Su In Heo3Ki Back Chu4Mi Suk Lee5Fu-Shi Quan6Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Parasitology, College of Medicine, Inje University, Busan 47392, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaMedical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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<sup>+</sup> 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. <b>Conclusions</b>: 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.https://www.mdpi.com/2076-393X/13/6/600orally dissolving filmvaccineinfluenza virusmucosal immunity
spellingShingle Keon-Woong Yoon
Jie Mao
Gi-Deok Eom
Su In Heo
Ki Back Chu
Mi Suk Lee
Fu-Shi Quan
Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus
Vaccines
orally dissolving film
vaccine
influenza virus
mucosal immunity
title Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus
title_full Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus
title_fullStr Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus
title_full_unstemmed Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus
title_short Orally Dissolving Film-Based Influenza Vaccines Confer Superior Protection Compared to the Oral Administration of Inactivated Influenza Virus
title_sort orally dissolving film based influenza vaccines confer superior protection compared to the oral administration of inactivated influenza virus
topic orally dissolving film
vaccine
influenza virus
mucosal immunity
url https://www.mdpi.com/2076-393X/13/6/600
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