Roe Shea K, Felter Brian, Zheng Bo, Ram Sanjay, Wetzler Lee M, Garges Eric, Zhu Tianmou, Genco Caroline A, Massari Paola
Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.
Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Vaccines (Basel). 2023 Dec 13;11(12):1846. doi: 10.3390/vaccines11121846.
Gonorrhea, a sexually transmitted disease caused by , 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 strains. The current study determined antigen recognition by human sera from -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 . 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.
淋病是一种由[病原体未提及]引起的性传播疾病,对全球公共卫生构成重大威胁。女性感染淋病可能没有症状,并可能导致严重的生殖并发症。抗生素耐药性不断升级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然难以捉摸。在回顾性流行病学研究中,基于脑膜炎球菌OMV的疫苗与淋病发病率降低有关,在小鼠阴道定植模型中与淋病奈瑟菌清除加速有关。交叉保护归因于共享抗原以及可能的交叉反应性杀菌抗体。我们使用基于人类黏膜感染期间淋病奈瑟菌转录组的候选抗原选择策略(CASS),确定了新的潜在疫苗靶点,这些靶点用于免疫小鼠时,可诱导产生针对[菌株未提及]菌株具有杀菌活性的抗体。本研究确定了淋病感染受试者血清中的抗原识别情况,评估了它们作为多抗原(组合)疫苗在小鼠中的潜力,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免疫反应成分导致抗体具有更好的杀菌活性。总之,源自CASS的抗原组合可能有望用于开发有效的淋病疫苗。