Steward M W, Sisley B M, Stanley C, Brown S E, Howard C R
Department of Medical Microbiology, London School of Hygiene and Tropical Medicine, UK.
Clin Exp Immunol. 1988 Jan;71(1):19-25.
The potential of a panel of synthetic HBsAg peptides as components of a synthetic hepatitis B vaccine was assessed. Each was used in turn as probes to analyse human immune responses to a licensed plasma-derived HBV vaccine. Both humoral and cellular responses were analysed with synthetic peptides representing residues 124-147 of the surface antigen of the virus (HBsAg) and residues 126-140 of the pre-S2 region. Antibody levels and affinities were assessed in radioimmunoassays with synthetic linear and cyclical forms of surface antigen peptides 124-137 and 139-147, with the gp30p25 polypeptide complex of HBsAg and with the linear pre-S2 peptide 126-140. Levels and affinities of antibodies to the antigens increased with time during immunization. However, antibodies binding the cyclical peptide representing amino acids 139 to 147 (C139) were present at higher levels and had higher affinities than were antibodies binding the other peptides, indicating that C139 more closely approximates a domain on the native antigen than do the other peptides. No humoral responses were measured with the pre-S2 peptide. Cellular responses were assessed by in vitro stimulation of peripheral blood lymphocytes by HBsAg and by the synthetic peptides. All vaccine recipients had demonstrable lymphocyte responsiveness to HBsAg after both second and third doses of the vaccine. Of the S and pre-S peptides used, only L124 failed to induce lymphocyte stimulation in all recipients. However, there were individual variations in both the time of initial responsiveness to peptides and in the level and time of maximal stimulation. Stimulation by native HBsAg particles, which corresponded to the appearance of anti-HBs antibody, preceded that observed using synthetic peptides. In all recipients, maximum stimulation indices with HBsAg were significantly higher than those observed with the peptides. In contrast to the absence of pre-S2 antibody, the lymphocytes from all recipients showed positive stimulation in response to the peptide representing residues 126-140 of the pre-S2 region. None of these individuals had antibodies to pre-S or an HB core peptide sequence nor did their lymphocytes respond to a synthetic peptide representing an HB core sequence.
评估了一组合成乙肝表面抗原（HBsAg）肽作为合成乙型肝炎疫苗成分的潜力。依次将每种肽用作探针，以分析人类对已获许可的血浆源性乙肝疫苗的免疫反应。使用代表病毒表面抗原（HBsAg）第124 - 147位残基和前S2区第126 - 140位残基的合成肽分析体液和细胞免疫反应。在放射免疫分析中，用表面抗原肽124 - 137和139 - 147的合成线性和环状形式、HBsAg的gp30p25多肽复合物以及线性前S2肽126 - 140评估抗体水平和亲和力。免疫期间，针对这些抗原的抗体水平和亲和力随时间增加。然而，与结合其他肽的抗体相比，结合代表氨基酸139至147的环状肽（C139）的抗体水平更高且亲和力更高，这表明C139比其他肽更接近天然抗原上的一个结构域。前S2肽未检测到体液免疫反应。通过用HBsAg和合成肽体外刺激外周血淋巴细胞来评估细胞免疫反应。在接种第二剂和第三剂疫苗后，所有疫苗接种者对HBsAg均表现出可检测到的淋巴细胞反应性。在所使用的S肽和前S肽中，只有L124未能在所有接种者中诱导淋巴细胞刺激。然而，对肽的初始反应时间以及最大刺激水平和时间存在个体差异。天然HBsAg颗粒的刺激先于使用合成肽观察到的刺激，且与抗HBs抗体的出现相对应。在所有接种者中，HBsAg的最大刺激指数显著高于使用肽观察到的刺激指数。与未检测到前S2抗体相反，所有接种者的淋巴细胞对代表前S2区第126 - 140位残基的肽均表现出阳性刺激。这些个体均无针对前S或乙肝核心肽序列的抗体，其淋巴细胞对代表乙肝核心序列的合成肽也无反应。
