Shewell Lucy K, Jen Freda E-C, Jennings Michael P
Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
PLoS One. 2017 Aug 3;12(8):e0182555. doi: 10.1371/journal.pone.0182555. eCollection 2017.
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.
多重耐药淋病奈瑟菌的出现迫切需要新的治疗方法或疫苗来预防淋球菌疾病。在本研究中，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其活性的潜力。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，功能性阻断抗体可能会阻止其定植和致病。基于AniA结构设计了覆盖活性位点附近区域的七种肽。七种肽缀合物中有六种产生了免疫反应。肽7（GALGQLKVEGAEN）能够引发能够阻断AniA活性的抗体。针对肽7缀合物产生的抗血清在20株淋病奈瑟菌临床分离株中检测到了AniA。本研究还评估了重组AniA蛋白抗原，并产生了高滴度的功能性阻断抗体反应。肽7缀合物或截短的重组AniA抗原具有被纳入抗淋病奈瑟菌疫苗的潜力。
