In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics.
In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics.
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通过转录组学鉴定的淋球菌三价候选疫苗的体外临床前评估
DOI：
10.3390/vaccines11121846
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发表时间：
2023-12-13
期刊：
影响因子：
7.8
通讯作者：
Massari P
中科院分区：
文献类型：
--
作者：
Roe SK;Felter B;Zheng B;Ram S;Wetzler LM;Garges E;Zhu T;Genco CA;Massari P
淋病是由淋病奈瑟菌引起的一种性传播疾病，对全球公共卫生构成重大威胁。女性感染可能无症状，但可能导致严重的生殖系统并发症。不断加剧的抗生素耐药性凸显了研发有效疫苗的必要性。正在探索的方法包括亚单位疫苗和外膜囊泡（OMV），但理想的候选疫苗仍未找到。基于脑膜炎球菌外膜囊泡的疫苗在回顾性流行病学研究中显示与淋病发病率降低有关，并且在小鼠阴道定植模型中可加速淋球菌的清除。交叉保护作用归因于共享抗原以及可能存在的交叉反应性杀菌抗体。利用基于人类黏膜感染期间淋球菌转录组的候选抗原选择策略（CASS），我们确定了新的潜在疫苗靶点，当用于免疫小鼠时，可诱导产生对淋病奈瑟菌菌株具有杀菌活性的抗体。当前的研究确定了淋病奈瑟菌感染受试者的人类血清对抗原的识别，评估了它们作为小鼠多抗原（组合）疫苗的潜力，并研究了不同佐剂（明矾或明矾 + MPLA）对淋病奈瑟菌功能性抗体反应的影响。我们的结果表明，明矾 + MPLA诱导的更强的Th1免疫反应成分可使抗体的杀菌活性提高。总之，CASS衍生抗原的组合对于开发有效的淋球菌疫苗可能具有前景。
Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, poses a significant global public health threat. Infection in women can be asymptomatic and may result in severe reproductive complications. Escalating antibiotic resistance underscores the need for an effective vaccine. Approaches being explored include subunit vaccines and outer membrane vesicles (OMVs), but an ideal candidate remains elusive. Meningococcal OMV-based vaccines have been associated with reduced rates of gonorrhea in retrospective epidemiologic studies, and with accelerated gonococcal clearance in mouse vaginal colonization models. Cross-protection is attributed to shared antigens and possibly cross-reactive, bactericidal antibodies. Using a Candidate Antigen Selection Strategy (CASS) based on the gonococcal transcriptome during human mucosal infection, we identified new potential vaccine targets that, when used to immunize mice, induced the production of antibodies with bactericidal activity against N. gonorrhoeae strains. The current study determined antigen recognition by human sera from N. gonorrhoeae-infected subjects, evaluated their potential as a multi-antigen (combination) vaccine in mice and examined the impact of different adjuvants (Alum or Alum+MPLA) on functional antibody responses to N. gonorrhoeae. Our results indicated that a stronger Th1 immune response component induced by Alum+MPLA led to antibodies with improved bactericidal activity. In conclusion, a combination of CASS-derived antigens may be promising for developing effective gonococcal vaccines.
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影响因子：
56.3
作者：
Abara, Winston E.;Bernstein, Kyle T.;Lewis, Felicia M. T.;Schillinger, Julia A.;Feemster, Kristen;Pathela, Preeti;Hariri, Susan;Islam, Aras;Eberhart, Michael;Cheng, Iris;Ternier, Alexandra;Slutsker, Jennifer Sanderson;Mbaeyi, Sarah;Madera, Robbie;Kirkcaldy, Robert D.
通讯作者：
Kirkcaldy, Robert D.
影响因子：
6.4
作者：
通讯作者：
--
影响因子：
11.8
作者：
Bruxvoort, Katia J.;Lewnard, Joseph A.;Qian, Lei
通讯作者：
Qian, Lei
影响因子：
7
作者：
El-Rami, Fadi E.;Zielke, Ryszard A.;Unemo, Magnus
通讯作者：
Unemo, Magnus
影响因子：
6.4
作者：
Gulati, Sunita;Mu, Xin;Rice, Peter A.
通讯作者：
Rice, Peter A.