中文摘要：大肠杆菌不耐热肠毒素重组B亚单元（LTB）是一种潜在的粘膜免疫佐剂。研究以肺炎支原体P97黏附素作为抗原分析以rLTB为佐剂构建的疫苗所诱导的体液免疫反应，并以氢氧化铝佐剂为对照，以此评估重组大肠杆菌不耐热肠毒素重组B亚单元rLTB作为肠道佐剂的应用潜力。结果表明，与对照组相比，以rLTBR1融合蛋白免疫小鼠能够近2倍的抗rR1免疫球蛋白；两种佐剂免疫小鼠都呈现出混合的Th1/Th2免疫反应，推测这可能是rR1介导的免疫反应，而不是佐剂；rLTBR1免疫组血清IgA的浓度比rR1-氢氧化铝组高1.5倍。该结果表明，与氢氧化铝相比，rLTB是一种强大的肠道佐剂，能够诱导产生更高的抗体滴度。
外文摘要：BACKGROUND The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.
外文关键词：aluminium hydroxide, humoral immune response, immune response modulation, rLTB, Mycoplasma hyopneumoniae, P97 adhesin
作者：da Cunha, CEP; Moreira, C; Rocha, ADR; Finger, PF; Magalhaes, CG; Ferreira, MRA; Dellagostin, OA; Moreira, AN; Conceicao, FR
作者单位：佩洛塔斯联邦大学
期刊名称：MEMORIAS DO INSTITUTO OSWALDO CRUZ
期刊影响因子：2.2
出版年份：2017
出版刊次：12
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