Research Article Engineered Flagellin-Based Adjuvant Boosts Mucosal Immunity in Recombinant RSV Vaccine
by Guoguo Ye1,2#, Changbin Qu3#, Zhi Liao4, Renxue Wu5, Ruoxu Liang2, Yuanxin Liu6, Jingjing Zou5, Yuanyuan Liu4, Shunjing Wang4, Linyi Yu6, Zhiyang Xing6, Shuai Wei2*, Wei Peng1,2*
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
2Guangzhou National Laboratory, Guangzhou 510005, China
3Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, Anhui, China
4School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China
5Institute of Pathogenic Biology, Hengyang Medical College; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China，Hengyang 421001, China
6Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan, 421001, China
#These authors contributed equally
*These authors contributed equally
*Corresponding authors: Wei Peng, Guangzhou National Laboratory, Guangzhou, China.
Shuai Wei, Guangzhou National Laboratory, Guangzhou, China.
Received Date: 24 September 2025
Accepted Date: 09 October 2025
Published Date: 13 October 2025
Citation: Ye G, Qu C, Liao Z, Wu R, Liang R, et al. (2025) Engineered Flagellin-Based Adjuvant Boosts Mucosal Immunity in Recombinant RSV Vaccine. Infect Dis Diag Treat 9: 280. https://doi.org/10.29011/2577-1515.100280
Abstract
Respiratory syncytial virus (RSV) infection is a global health concern that poses a significant threat to children under the age of five. Yet vaccine development has been hindered by historical safety concerns, including vaccine-associated enhanced respiratory disease (VAERD). To address these challenges, we rationally engineered a soluble, stable, and deimmunized flagellin-derived adjuvant (FIC) to activated mucosal immunity, which plays a critical role in protecting against respiratory diseases and is considered safe for children. In mouse models, FIC adjuvanted RSV prefusion F (pre-F) vaccines elicited a Th1-biased immune response, characterized by elevated expression levels of IFN-γ, IL-2, and TNF-α and robust pre-F-specific humoral, cellular, and mucosal immunity, while minimizing flagellin-associated immunogenicity. Further, a sequential immunization regimen incorporating FIC significantly enhanced protection against both upper and lower respiratory tract RSV challenges. Notably, intranasal sequential immunization induced an RSV pre-F specific IgG-IgA class switch and enhanced cellular immune responses, thereby optimizing the vaccine's efficacy against RSV. These findings indicated that structure-guided adjuvant optimization combined with mucosal prime-boost strategies can overcome historical barriers in RSV vaccinology, offering a promising pathway for respiratory pathogen vaccine development.
Keywords: Flagellin adjuvant, Structural optimization, Triple immunization, RSV vaccine, Sequential vaccination
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