title: Immunoprotectivity of HLA-A2 CTL peptides derived from respiratory syncytial virus fusion protein in HLA-A2 transgenic mouse.
abstract: Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33-41), 13 (F214-222), 14 (F273-281), and 23 (F559-567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine.
authors: Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan, Republic of China.
authors: Hsiao-Yun
authors: HY
authors: Shao
authors: Yi-Wen
authors: YW
authors: Lin
authors: Shu-Ling
authors: SL
authors: Yu
authors: Hsiang-Yin
authors: HY
authors: Lin
authors: Ebenezer
authors: E
authors: Chitra
authors: Yung-Chen
authors: YC
authors: Chang
authors: Charles
authors: C
authors: Sia
authors: Pele
authors: P
authors: Chong
authors: Ming-Tao
authors: MT
authors: Hsu
authors: Olivia L
authors: OL
authors: Wei
authors: Yen-Hung
authors: YH
authors: Chow
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004274:DNA, Recombinant / Q000235:genetics; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D016207:Cytokines; D004274:DNA, Recombinant; D000939:Epitopes; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; D014765:Viral Vaccines