School of Medicine and Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Clin Infect Dis. 2011 Jan 1;52(1):70-7. doi: 10.1093/cid/ciq065.
Natural immunity to Neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as Neisseria lactamica.
We enrolled 61 students with no current carriage of Neisseria species and inoculated them intranasally with 10,000 colony-forming units of Neisseria lactamica or sham control. Colonization was monitored in oropharyngeal samples over 6 months. We measured specific mucosal and systemic antibody responses to N. lactamica and serum bactericidal antibody (SBA) and opsonophagocytic antibodies to a panel of N. meningitidis serogroup B strains. We also inoculated an additional cohort following vaccination with N. lactamica outer-membrane vesicles (OMV) produced from the same strain.
Twenty-six (63.4%) of 41 inoculated individuals became colonized with N. lactamica; 85% remained colonized at 12 weeks. Noncarriers were resistant to rechallenge, and carriers who terminated carriage were relatively resistant to rechallenge. No carriers acquired N. meningitidis carriage over 24 weeks, compared with 3 control subjects (15%). Carriers developed serum IgG and salivary IgA antibodies to the inoculated N. lactamica strain by 4 weeks; noncarriers and control subjects did not. Cross-reactive serum bactericidal antibody responses to N.meningitidis were negligible in carriers, but they developed broad opsonophagocytic antimeningococcal antibodies. OMV vaccinees developed systemic and mucosal anti-N. lactamica antibodies and were relatively resistant to N. lactamica carriage but not to natural acquisition of N. meningitidis.
Carriers of N. lactamica develop mucosal and systemic humoral immunity to N. lactamica together with cross-reacting systemic opsonophagocytic but not bactericidal antibodies to N. meningitidis. Possession of humoral immunity to N. lactamica inhibits acquisition of N. lactamica but not of N. meningitidis. Some individuals are intrinsically resistant to N. lactamica carriage, independent of humoral immunity.
对脑膜炎奈瑟菌的天然免疫可能来自于鼻咽部携带密切相关的共生菌，如奈瑟氏乳酸奈瑟菌。
我们招募了 61 名目前没有携带奈瑟菌的学生，并用 10000 个菌落形成单位的奈瑟氏乳酸奈瑟菌或假对照物经鼻接种。在 6 个月内监测口咽样本中的定植情况。我们测量了针对 N. lactamica 的特定粘膜和系统抗体反应以及针对一组脑膜炎奈瑟菌 B 群血清杀菌抗体（SBA）和调理吞噬抗体。我们还在接种了相同菌株的奈瑟氏乳酸奈瑟菌外膜囊泡（OMV）疫苗后，接种了另一组人群。
41 名接种者中有 26 名（63.4%）定植了 N. lactamica；85%在 12 周时仍定植。未携带的个体对再挑战具有抗性，而终止携带的携带者对再挑战相对具有抗性。在 24 周内，没有携带者获得脑膜炎奈瑟菌的携带，而对照组中有 3 名（15%）携带者。接种后 4 周，携带者产生了针对接种的 N. lactamica 菌株的血清 IgG 和唾液 IgA 抗体；未携带的个体和对照组没有。载体对 N.meningitidis 的交叉反应性血清杀菌抗体反应可以忽略不计，但它们产生了广泛的调理吞噬抗脑膜炎奈瑟菌抗体。OMV 疫苗接种者产生了针对 N. lactamica 的系统和粘膜抗体，对 N. lactamica 携带具有相对抗性，但不能自然获得 N. meningitidis。
携带 N. lactamica 的个体对 N. lactamica 产生了粘膜和系统体液免疫，同时对 N. meningitidis 产生了交叉反应性的系统调理吞噬但无杀菌抗体。对 N. lactamica 的体液免疫抑制了 N. lactamica 的获得，但不能抑制 N. meningitidis 的获得。一些个体对 N. lactamica 的携带具有内在抗性，与体液免疫无关。
