Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen.
Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen.
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DOI：
10.1016/j.jconrel.2011.11.009
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发表时间：
2012-03-10
期刊：
影响因子：
--
通讯作者：
McKay PF
中科院分区：
文献类型：
--
作者：
Mann JF;Stieh D;Klein K;de Stegmann DS;Cranage MP;Shattock RJ;McKay PF
通过黏膜接种而不使用炎性佐剂来产生有效的免疫反应，从而破坏上皮屏障并招募新的细胞靶点，是旨在防止性获得性病原体的疫苗的一个关键目标。在本研究中，我们使用一种模型HIV抗原(CN54gp140)与转铁蛋白(Tf)偶联，并评估天然转铁蛋白受体CD71调节免疫的能力。我们发现，结合的转铁蛋白与其受体保持着高的亲和力，并且结合物被特异性地转运穿过上皮屏障，与粘膜下基质中的MHC Class II+细胞共同定位。对小鼠的免疫研究表明，当结合物局部应用于鼻粘膜时，TF-gp140结合物可诱导高滴度的CN54gp140特异性血清抗体，相当于系统接种，而仅gp140具有较低的免疫原性。此外，Tf-gp140结合物可同时激发免疫球蛋白和免疫球蛋白A反应，且女性生殖道中gp140特异性免疫球蛋白A滴度显著高于未结合抗原。这些反应是在没有任何促炎佐剂的情况下，单独在粘膜应用结合蛋白后实现的，这表明了一种潜在的有用和新颖的分子靶向方法，即递送疫苗直接诱导或增强病原体特异性粘膜免疫。一步一步地说明了利用细胞穿透的高活性生物学过程作为粘膜疫苗靶向和增强免疫原性。
The generation of effective immune responses by mucosal vaccination without the use of inflammatory adjuvants, that compromise the epithelial barrier and recruit new cellular targets, is a key goal of vaccines designed to protect against sexually acquired pathogens. In the present study we use a model HIV antigen (CN54gp140) conjugated to transferrin (Tf) and evaluate the ability of the natural transferrin receptor CD71 to modulate immunity. We show that the conjugated transferrin retained high affinity for its receptor and that the conjugate was specifically transported across an epithelial barrier, co-localizing with MHC Class II+ cells in the sub-mucosal stroma. Vaccination studies in mice revealed that the Tf-gp140 conjugate elicited high titres of CN54gp140-specific serum antibodies, equivalent to a systemic vaccination, when conjugate was applied topically to the nasal mucosae whereas gp140 alone was poorly immunogenic. Moreover, the Tf-gp140 conjugate elicited both IgG and IgA responses and significantly higher gp140-specific IgA titre in the female genital tract than unconjugated antigen. These responses were achieved after mucosal application of the conjugated protein alone, in the absence of any pro-inflammatory adjuvant and suggest a potentially useful and novel molecular targeting approach, delivering a vaccine cargo to directly elicit or enhance pathogen-specific mucosal immunity. A stepwise illustration of the utilization of the highly active biological process of transcytosis for mucosal vaccine targeting and enhanced immunogenicity.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1126/science.1183021
发表时间：
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期刊：
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影响因子：
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通讯作者：
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DOI：
10.1590/s0074-02762011000900021
发表时间：
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期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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