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基于霍乱弧菌O1小川型脂多糖抗原的复合偶联物的免疫学特性。

Immunological properties of complex conjugates based on Vibrio cholerae O1 Ogawa lipopolysaccharide antigen.

作者信息

Paulovicová E, Machová E, Hostacká A, Bystrický S

机构信息

Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic.

出版信息

Clin Exp Immunol. 2006 Jun;144(3):521-7. doi: 10.1111/j.1365-2249.2006.03077.x.

Abstract

Host protection by humoral immunity against Vibrio cholerae O1 confers lipopolysaccharide (LPS)-specific vibriocidal antibodies. Levels of relevant specific antibodies are closely related to complement-mediated inactivation of the vibrios inoculum, especially on the mucosal surface of intestine. We have tested complex V. cholerae O1 Ogawa-detoxified lipopolysaccharide (dLPS) conjugates. The first conjugate contained glucan both as the immunomodulator and the matrix; the second conjugate contained immunologically inert amylose as matrix. Both d-LPS conjugates contain multiply attached dLPS antigen. These conjugates elicited a statistically significant increase of antigen-specific IgG levels in mice (P<0.001 and P<0.05, respectively). The specific anti-conjugate IgG and IgA response after the second (booster) dose were significantly higher compared to pre-immune and whole-cell response. The most effective vibriocidal activity was observed in the case of conjugate, with glucan as the matrix. The highest correlation was found between vibriocidal activity and specific IgG2b (r=0.765) and IgA (r=0.887) sera levels. The determination of specific IgG subclasses and IgG2a + 2b/IgG1 ratio revealed a dominant T(H)1 cell response crucial for effective vaccine candidate.

摘要

通过体液免疫对霍乱弧菌O1的宿主保护作用可产生脂多糖(LPS)特异性杀弧菌抗体。相关特异性抗体的水平与补体介导的接种弧菌的失活密切相关,尤其是在肠道黏膜表面。我们测试了霍乱弧菌O1小川型解毒脂多糖(dLPS)复合物。第一种复合物含有葡聚糖作为免疫调节剂和基质;第二种复合物含有免疫惰性的直链淀粉作为基质。两种d-LPS复合物都含有多个连接的dLPS抗原。这些复合物在小鼠体内引起了抗原特异性IgG水平的统计学显著升高(分别为P<0.001和P<0.05)。第二次(加强)剂量后的特异性抗复合物IgG和IgA反应与免疫前和全细胞反应相比显著更高。在以葡聚糖为基质的复合物中观察到了最有效的杀弧菌活性。在杀弧菌活性与特异性IgG2b(r=0.765)和IgA(r=0.887)血清水平之间发现了最高的相关性。特异性IgG亚类以及IgG2a + 2b/IgG1比值的测定揭示了对于有效的候选疫苗至关重要的占主导地位的T(H)1细胞反应。

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