人呼吸道合胞病毒SH蛋白混合多肽免疫原性初步研究

Preliminary Studies on the Immunogenicity of A Mixed Peptide from the SH Protein of the Human Respiratory Syncytial Virus

本研究旨在探讨人呼吸道合胞病毒(Human respiratory syncytial virus,HRSV)小疏水蛋白(Small hydrophobic protein,SH)T细胞表位肽的免疫原性和保护效果。通过设计并合成覆盖SH蛋白序列全长的10条多肽,利用HRSV感染小鼠的脾淋巴细胞进行IFN-γ-酶联免疫斑点(Enzyme-linked immunospot assay, ELISpot)的检测,筛选出5条能显著刺激IFN-γ产生的SH蛋白T细胞表位多肽。将其与CpG和磷酸铝(AL)佐剂配制成混合多肽疫苗,两次皮下给药的方式免疫C57BL/6J小鼠,评价其免疫原性和保护效果。结果显示,与佐剂对照组相比,SH蛋白混合多肽疫苗可以诱导免疫后的小鼠产生抗原特异性IgG抗体和Th1偏向的T细胞免疫应答,降低HRSV感染后肺病毒载量,并减轻肺脏病理损伤。研究结果表明,SH蛋白混合多肽通过免疫小鼠可以引起良好的免疫原性,并保护小鼠抵抗HRSV的感染。为进一步研究基于SH蛋白的HRSV多肽疫苗提供了科学依据。

The objective of this study was to investigate the immunogenicity and protective effects of the T-cell epitope peptide of human respiratory syncytial virus(HRSV)small hydrophobic protein(SH).Ten peptides covering the full length of the SH protein sequence were designed and synthesized.Using splenic lymphocytes from HRSV-infected mice,five T-cell epitope peptides of SH protein that significantly stimulated interferon-,(IFN-)production were screened by IFN-γ-Enzyme-Linked Immunospot Assay(ELISpot).The peptides were used to create a mixed peptide vaccine,which was administered subcutaneously twice to C57BL/6J mice along with 5′cytosine-phosphate-guanine 3′oligonucleotide(CpG-OND)and aluminum phosphate(AL)adjuvant.The purpose was to evaluate the vaccine's immunogenicity and protective effect.This study found that the SH protein hybrid peptide vaccine elicited antigen-specific IgG antibodies and T helper 1 cell(Th1)biased T-cell immune responses in immunized mice,compared to the adjuvant control group.Additionally,it reduced the lung viral load and attenuated the pathological damage of the lungs after HRSV infection.These results demonstrate that SH protein peptides can effectively induce immunogenicity and protect mice against HRSV infection.This provides a scientific basis for further research on HRSV peptide vaccines based on SH protein.