PMID- 38250890 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240129 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 12 IP - 1 DP - 2024 Jan 12 TI - A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice. LID - 10.3390/vaccines12010077 [doi] LID - 77 AB - Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors' PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine. FAU - Guo, Hong AU - Guo H AUID- ORCID: 0009-0000-9826-4044 AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Song, Yang AU - Song Y AUID- ORCID: 0000-0002-7053-3836 AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Li, Hai AU - Li H AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Hu, Hongqiao AU - Hu H AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Shi, Yuqing AU - Shi Y AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Jiang, Jie AU - Jiang J AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Guo, Jinyuan AU - Guo J AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Cao, Lei AU - Cao L AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Mao, Naiying AU - Mao N AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. FAU - Zhang, Yan AU - Zhang Y AD - NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. AD - National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. LA - eng PT - Journal Article DEP - 20240112 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC10820450 OTO - NOTNLM OT - T-cell epitope OT - human respiratory syncytial virus OT - peptide vaccine COIS- We do not have conflicts of interest associated with this publication, and there has been no financial support for this work that could have influenced its outcome. This manuscript is original, has not been previously published, and is not currently under consideration by another journal. EDAT- 2024/01/22 06:42 MHDA- 2024/01/22 06:43 PMCR- 2024/01/12 CRDT- 2024/01/22 05:35 PHST- 2023/12/08 00:00 [received] PHST- 2024/01/04 00:00 [revised] PHST- 2024/01/10 00:00 [accepted] PHST- 2024/01/22 06:43 [medline] PHST- 2024/01/22 06:42 [pubmed] PHST- 2024/01/22 05:35 [entrez] PHST- 2024/01/12 00:00 [pmc-release] AID - vaccines12010077 [pii] AID - vaccines-12-00077 [pii] AID - 10.3390/vaccines12010077 [doi] PST - epublish SO - Vaccines (Basel). 2024 Jan 12;12(1):77. doi: 10.3390/vaccines12010077.