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B 群脑膜炎球菌疫苗 Bexsero 可诱导针对淋病奈瑟菌的抗体。

The Serogroup B Meningococcal Vaccine Bexsero Elicits Antibodies to Neisseria gonorrhoeae.

机构信息

Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.

Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, United Kingdom.

出版信息

Clin Infect Dis. 2019 Sep 13;69(7):1101-1111. doi: 10.1093/cid/ciy1061.

Abstract

BACKGROUND

Neisseria gonorrhoeae and Neisseria meningitidis are closely-related bacteria that cause a significant global burden of disease. Control of gonorrhoea is becoming increasingly difficult, due to widespread antibiotic resistance. While vaccines are routinely used for N. meningitidis, no vaccine is available for N. gonorrhoeae. Recently, the outer membrane vesicle (OMV) meningococcal B vaccine, MeNZB, was reported to be associated with reduced rates of gonorrhoea following a mass vaccination campaign in New Zealand. To probe the basis for this protection, we assessed the cross-reactivity to N. gonorrhoeae of serum raised to the meningococcal vaccine Bexsero, which contains the MeNZB OMV component plus 3 recombinant antigens (Neisseria adhesin A, factor H binding protein [fHbp]-GNA2091, and Neisserial heparin binding antigen [NHBA]-GNA1030).

METHODS

A bioinformatic analysis was performed to assess the similarity of MeNZB OMV and Bexsero antigens to gonococcal proteins. Rabbits were immunized with the OMV component or the 3 recombinant antigens of Bexsero, and Western blots and enzyme-linked immunosorbent assays were used to assess the generation of antibodies recognizing N. gonorrhoeae. Serum from humans immunized with Bexsero was investigated to assess the nature of the anti-gonococcal response.

RESULTS

There is a high level of sequence identity between MeNZB OMV and Bexsero OMV antigens, and between the antigens and gonococcal proteins. NHBA is the only Bexsero recombinant antigen that is conserved and surfaced exposed in N. gonorrhoeae. Bexsero induces antibodies in humans that recognize gonococcal proteins.

CONCLUSIONS

The anti-gonococcal antibodies induced by MeNZB-like OMV proteins could explain the previously-seen decrease in gonorrhoea following MeNZB vaccination. The high level of human anti-gonococcal NHBA antibodies generated by Bexsero vaccination may provide additional cross-protection against gonorrhoea.

摘要

背景

淋病奈瑟菌和脑膜炎奈瑟菌是密切相关的细菌,它们在全球范围内造成了巨大的疾病负担。由于广泛的抗生素耐药性,淋病的控制变得越来越困难。虽然脑膜炎球菌疫苗已常规用于预防脑膜炎奈瑟菌感染,但目前尚无针对淋病奈瑟菌的疫苗。最近,在新西兰大规模疫苗接种运动后,报道称外膜囊泡(OMV)脑膜炎球菌 B 疫苗 MeNZB 与淋病发病率降低有关。为了探究这种保护作用的基础,我们评估了针对包含 MeNZB OMV 成分和 3 种重组抗原(奈瑟菌黏附素 A、因子 H 结合蛋白[ fHbp]-GNA2091 和奈瑟菌肝素结合抗原[ NHBA]-GNA1030)的脑膜炎球菌疫苗 Bexsero 产生的血清对淋病奈瑟菌的交叉反应性。

方法

进行了生物信息学分析,以评估 MeNZB OMV 和 Bexsero 抗原与淋病奈瑟菌蛋白的相似性。用 OMV 成分或 Bexsero 的 3 种重组抗原免疫兔子,并用 Western blot 和酶联免疫吸附试验评估识别淋病奈瑟菌的抗体产生情况。检测接种 Bexsero 的人类血清以评估抗淋病奈瑟菌反应的性质。

结果

MeNZB OMV 和 Bexsero OMV 抗原之间以及抗原与淋病奈瑟菌蛋白之间存在高度的序列同一性。NHBA 是 Bexsero 重组抗原中唯一在淋病奈瑟菌中保守且表面暴露的抗原。Bexsero 诱导人类产生的抗体可识别淋病奈瑟菌蛋白。

结论

MeNZB 样 OMV 蛋白诱导的抗淋病奈瑟菌抗体可以解释之前在 MeNZB 疫苗接种后淋病发病率下降的情况。Bexsero 接种诱导的高水平人类抗淋病奈瑟菌 NHBA 抗体可能为淋病提供额外的交叉保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/6743822/d10be4f556e1/ciy1061f0001.jpg

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