佐剂对疫苗诱导的体液反应和致病性奈瑟氏菌鼻腔和生殖器定植临床前模型的保护作用的影响

Epshita A. Islam, Jamie E. Fegan, Joseph J. Zeppa, Sang K. Ahn, Dixon Ng, Elissa G. Currie, Jessica Lam, Trevor F. Moraes, Scott D. Gray-Owen
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引用次数: 0

摘要

引起性传播感染淋病的淋病奈瑟菌和引起细菌性脑膜炎和败血症的脑膜炎奈瑟菌是密切相关的人类限制性病原体,它们栖息在不同的初级粘膜壁龛中。虽然针对侵袭性脑膜炎球菌疾病的成功疫苗已问世数十年,但抗生素耐药性的迅速增加导致人们迫切需要开发一种有效的淋球菌疫苗。这两种病原体共有几种表面抗原,因此跨物种保护的前景令人振奋。然而,疫苗介导的免疫反应类型对呼吸道感染和生殖器感染的保护作用尚不明确。在本研究中,我们利用淋病双球菌在雌性下生殖道定植和脑膜炎双球菌在上呼吸道定植的成熟小鼠模型,研究了转铁蛋白结合蛋白 B(TbpB)疫苗与免疫学上不同的疫苗佐剂的性能。我们证明,疫苗介导的保护作用受佐剂选择的影响,Th1/2平衡佐剂对淋球菌的保护作用最佳,而Th1/2平衡佐剂和Th2倾斜佐剂都能显著减少脑膜炎双球菌的负担。我们进一步证实,保护状态与体液反应或杀菌滴度之间缺乏相关性。综合来看,这项工作证明了单一疫苗制剂实现泛鼻孢子菌覆盖的可行性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adjuvant-dependent impacts on vaccine-induced humoral responses and protection in preclinical models of nasal and genital colonization by pathogenic Neisseria
Neisseria gonorrhoeae, which causes the sexually transmitted infection gonorrhea and N. meningitidis, a leading cause of bacterial meningitis and septicemia, are closely related human-restricted pathogens that inhabit distinct primary mucosal niches. While successful vaccines against invasive meningococcal disease have been available for decades, the rapid rise in antibiotic resistance has led to an urgent need to develop an effective gonococcal vaccine. Several surface antigens are shared among these two pathogens, making cross-species protection an exciting prospect. However, the type of vaccine-mediated immune response required to achieve protection against respiratory versus genital infection remains ill defined. In this study, we utilize well established mouse models of female lower genital tract colonization by N. gonorrhoeae and upper respiratory tract colonization by N. meningitidis to examine the performance of transferrin binding protein B (TbpB) vaccines formulated with immunologically distinct vaccine adjuvants. We demonstrate that vaccine-mediated protection is influenced by the choice of adjuvant, with Th1/2-balanced adjuvants performing optimally against N. gonorrhoeae, and both Th1/2-balanced and Th2-skewing adjuvants leading to a significant reduction in N. meningitidis burden. We further establish a lack of correlation between protection status and the humoral response or bactericidal titre. Combined, this work provides supports the feasibility for a single vaccine formulation to achieve pan-neisserial coverage.
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