以霍乱毒素重组B亚单位为佐剂的流感抗原滴鼻免疫效果研究

Intranasal Administration of Trivalent Influenza Virus with rCTB on Mice

研究霍乱毒素重组B亚单位(recombinant cholera toxin B subunit,rCTB)为佐剂的流感抗原滴鼻免疫小鼠后,小鼠的体液免疫和局部黏膜免疫反应。三价流感病毒灭活抗原及裂解抗原按比例与rCTB配伍,滴鼻免疫小鼠,分析血清中IgG和IgM的动态变化,二免三周后,分析血清中HAI的变化,收集鼻、肺冲洗液,分析IgG和sIgA的变化。结果表明:全病毒组及rCTB+裂解抗原组各项指标变化较明显,小鼠血清IgG和IgM在二免三周后仍维持在较高的水平,而其他两组均呈下降趋势;全病毒组鼻、肺冲洗液IgG和sIgA抗体滴度以及血清HAI抗体滴度均高于rCTB+全病毒组(P<0.01),而rCTB+裂解抗原组鼻、肺冲洗液IgG和sIgA抗体滴度以及血清HAI抗体滴度明显高于裂解抗原组(P<0.01)。研究表明:以全病毒抗原及rCTB+裂解抗原滴鼻免疫小鼠,均可诱导小鼠产生较强的系统免疫反应和局部黏膜免疫反应。rCTB与流感裂解抗原配伍滴鼻,可提高抗原的免疫原性,增强机体的黏膜免疫应答反应。

To study the systemic and mucosal antibody response induced by i. n. trivalent whole influenza virus （wFlu） and trivalent split influenza virus （sFlu） with rCTB. wFlu and sFlu was formulated with rCTB, administered intranasal （i. n. ）. Mice sera were collected from 0 day to 28 day post i. n. Changes of serum IgG and IgM were observed, as well as the titres of hemagglutination inhibition （HAI） and specific IgG and sIgA in lung and nasal washes were determined. The result showed that the mice i.n. with rCTB-wFlu and rCTB-sFlu changed obviously. In brief, the wFlu and rCTB-sFlu elicited high titres of serum IgG, and IgM and maintained high level post 28d, whereas the others decreased post 28d. In addition, i.n. with wFlu induced significant higher titres of HAI and specific IgG and sIgA in lung and nasal washes than rCTB-wFlu, but the rCTB-sFlu induced significant higher titres of HAI and specific IgG and sIgA in lung and nasal washes than sFlu. I.n. with wFlu or rCTB sFlu might elicit systemic and mucosal immunoresponse. And rCTB are a potent mucosal adjuvants for split influenza vaccines.