Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: Influence of the menstrual cycle
Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: Influence of the menstrual cycle
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DOI：
10.4049/jimmunol.169.1.566
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发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Neutra, MR
中科院分区：
文献类型：
--
作者：
Kozlowski, PA;Williams, SB;Neutra, MR
用灭活弧菌和霍乱毒素B亚单位（CT B）组成的霍乱疫苗，比较粘膜免疫途径诱导全身和粘膜抗体的效果。四组妇女在卵泡期（V-FPimm）或黄体期（V-LPimm）月经周期阶段通过直肠免疫（R-imm）途径、鼻免疫（N-imm）途径或阴道免疫途径进行三次每月免疫。用10倍更少的疫苗进行N-imm，以确定通过该途径施用更少的Ag是否可以如在啮齿动物中那样产生与由更高剂量R-imm或阴道免疫诱导的粘膜Ab应答相当的粘膜Ab应答。用ELISA法测定血清和分泌物中诱导的抗体浓度。这些途径均未产生持久的唾液Ab应答。N-imm在血清中诱导最高水平的CTB特异性IgG。R-imm不能在生殖道分泌物中产生CTB特异性IgA。N-imm、V-FPimm和V-LPimm均产生宫颈CTB特异性IgA应答，其幅度和频率相当。然而，只有V-FPimm诱导宫颈IgA 2限制性抗体的细菌LPS疫苗组分。V-FPimm，但不是V-LPimm，也诱导CTB特异性IgA在直肠分泌物。N-imm产生直肠CTB特异性IgA的能力上级于V-FPimm，但R-imm妇女直肠分泌物中CTB特异性IgA和LPS特异性IgA、IgG和IgM Ab的量最大。这些数据表明，在女性中，单独使用N-imm可在血清、生殖道和直肠中诱导特异性Ab。然而，局部V-FPimm或R-imm产生的生殖道和直肠Ab应答的诱导可能需要给予极高剂量的鼻用疫苗。
A cholera vaccine containing killed vibrios and cholera toxin B subunit (CTB) was used to compare mucosal immunization routes for induction of systemic and mucosal Ab. Four groups of women were given three monthly immunizations by the rectal immunization (R-imm) route, nasal immunization (N-imm) route, or vaginal immunization route during either the follicular (V-FPimm) or luteal (V-LPimm) menstrual cycle phase. N-imm was performed with 10-fold less vaccine to determine if administration of less Ag by this route can, as in rodents, produce mucosal Ab responses comparable to those induced by higher dose R-imm or vaginal immunization. Concentrations of Ab induced in sera and secretions were measured by ELISA. None of these routes produced durable salivary Ab responses. N-imm induced greatest levels of CTB-specific IgG in sera. R-imm failed to generate CTB-specific IgA in genital tract secretions. N-imm, V-FPimm, and V-LPimm all produced cervical CTB-specific IgA responses comparable in magnitude and frequency. However, only V-FPimm induced cervical IgA2-restricted Ab to the bacterial LPS vaccine component. V-FPimm, but not V-LPimm, also induced CTB-specific IgA in rectal secretions. N-imm was superior to V-FPimm for producing rectal CTB-specific IgA, but the greatest amounts of CTB-specific IgA and LPS-specific IgA, IgG, and IgM Ab were found in rectal secretions of R-imm women. These data suggest that in women, N-imm alone could induce specific Ab in serum, the genital tract, and rectum. However, induction of genital tract and rectal Ab responses of the magnitude generated by local V-FPimm or R-imm will likely require administration of comparably high nasal vaccine dosages.