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首页> 外文期刊>Infection and immunity >Production of Nontypeable Haemophilus influenzae HtrA by Recombinant Bordetella pertussis with the Use of Filamentous Hemagglutinin as a Carrier
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Production of Nontypeable Haemophilus influenzae HtrA by Recombinant Bordetella pertussis with the Use of Filamentous Hemagglutinin as a Carrier

机译：重组百日咳博德特氏菌以丝状血凝素为载体生产非典型流感嗜血杆菌HtrA

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Bordetella pertussis, the etiologic agent of whooping cough, is a highly infectious human pathogen capable of inducing mucosal and systemic immune responses upon a single intranasal administration. In an attenuated, pertussis toxin (PTX)-deficient recombinant form, it may therefore constitute an efficient bacterial vector that is particularly well adapted for the delivery of heterologous antigens to the respiratory mucosa. Filamentous hemagglutinin (FHA) has been used as a carrier to present foreign antigens at the bacterial surface, thereby inducing local, systemic, and protective immune responses to these antigens in mice. Both full-length and truncated (Fha44) forms of FHA have been used for antigen presentation. To investigate the effect of the carrier (FHA or Fha44) on antibody responses to passenger antigens, we genetically fused the HtrA protein of nontypeable Haemophilus influenzae to either FHA form. The fha-htrA and Fha44 gene-htrA hybrids were expressed as single copies inserted into the chromosome of PTX-deficient B. pertussis. Both chimeras were secreted into the culture supernatants of the recombinant strains and were recognized by anti-FHA and anti-HtrA antibodies. Intranasal infection with the strain producing the FHA-HtrA hybrid led to significantly higher anti-HtrA and anti-FHA antibody titers than those obtained in mice infected with the Fha44-HtrA-producing strain. Interestingly, the B. pertussis strain producing the Fha44-HtrA chimera colonized the mouse lungs more efficiently than the parental, Fha44-producing strain and gave rise to higher anti-FHA antibody titers than those induced by the parental strain.
机译：百日咳百日咳百日咳是一种高度传染性的人类病原体，单次鼻内给药可诱导粘膜和全身免疫反应。因此，在减毒的百日咳毒素（PTX）缺陷型重组形式中，它可以构成有效的细菌载体，特别适合于将异源抗原递送至呼吸道粘膜。丝状血凝素（FHA）已被用作在细菌表面呈递外来抗原的载体，从而在小鼠中诱导对这些抗原的局部，全身和保护性免疫应答。 FHA的全长和截短形式（Fha44）都已用于抗原呈递。为了研究载体（FHA或Fha44）对客体抗原的抗体应答的影响，我们将不可分型的流感嗜血杆菌的HtrA蛋白遗传融合到两种FHA形式上。将 fha-htrA 和Fha44基因 -htrA 杂种表达为插入PTX缺陷型 B染色体的单拷贝。百日咳。两种嵌合体均分泌到重组菌株的培养上清液中，并被抗FHA和抗HtrA抗体识别。鼻内感染产生FHA-HtrA杂种的菌株导致的抗HtrA和抗FHA抗体滴度明显高于感染Fha44-HtrA的菌株的小鼠。有趣的是， B。产生Fha44-HtrA嵌合体的百日咳菌株比产生Fha44的亲本菌株更有效地定居小鼠肺部，并产生比亲本菌株诱导的抗体更高的抗FHA抗体效价。

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