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Refinement of immunizing antigens to produce functional blocking antibodies against the AniA nitrite reductase of Neisseria gonorrhoeae

机译:细化免疫抗原以产生针对淋病奈瑟氏球菌AniA亚硝酸还原酶的功能性封闭抗体

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摘要

The emergence of multi-drug resistant Neisseria gonorrhoeae has generated an urgent need for novel therapies or a vaccine to prevent gonococcal disease. In this study we investigate the potential of targeting the surface exposed nitrite reductase, AniA, to block activity by producing functional blocking antibodies. AniA activity is essential for anaerobic growth and biofilm formation of N. gonorrhoeae and functional blocking antibodies may prevent colonisation and disease. Seven peptides covering regions adjacent to the active site were designed based on the AniA structure. Six of the seven peptide conjugates generated immune responses. Peptide 7, GALGQLKVEGAEN, was able to elicit antibodies capable of blocking AniA activity. Antiserum raised against the peptide 7 conjugate detected AniA in 20 N. gonorrhoeae clinical isolates. Recombinant AniA protein antigens were also assessed in this study and generated high-titre, functional blocking antibody responses. Peptide 7 conjugates or truncated recombinant AniA antigens have potential for inclusion in a vaccine against N. gonorrhoeae.
机译:耐多药性淋病奈瑟氏球菌的出现迫切需要新的疗法或疫苗来预防淋球菌病。在这项研究中,我们研究了靶向表面暴露的亚硝酸还原酶AniA通过产生功能性阻断抗体来阻断活性的潜力。 AniA活性对于淋病奈瑟菌的厌氧生长和生物膜形成至关重要,而功能性阻断抗体可能会阻止定植和疾病。基于AniA结构设计覆盖活性位点附近区域的七个肽。七个肽缀合物中的六个产生了免疫反应。肽7(GALGQLKVEGAEN)能够引发能够阻断AniA活性的抗体。针对肽7共轭物产生的抗血清在20株淋病奈瑟氏球菌临床分离物中检测到AniA。在这项研究中还评估了重组AniA蛋白抗原,并产生了高滴度,功能性阻断抗体反应。肽7结合物或截短的重组AniA抗原具有潜在的抗淋病奈瑟氏球菌疫苗的能力。

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