Plested Joyce S, Welsch Jo Anne, Granoff Dan M
Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
Clin Vaccine Immunol. 2009 Jun;16(6):785-91. doi: 10.1128/CVI.00007-09. Epub 2009 Apr 1.
The binding of complement factor H (fH) to meningococci was recently found to be specific for human fH. Therefore, passive protective antibody activity measured in animal models of meningococcal bacteremia may overestimate protection in humans, since in the absence of bound fH, complement activation is not downregulated. We developed an ex vivo model of meningococcal bacteremia using nonimmune human blood to measure the passive protective activity of stored sera from 36 adults who had been immunized with an investigational meningococcal multicomponent recombinant protein vaccine. Before immunization, human complement-mediated serum bactericidal activity (SBA) titers of > or = 1:4 against group B strains H44/76, NZ98/254, and S3032 were present in 19, 11, and 8% of subjects, respectively; these proportions increased to 97, 22, and 36%, respectively, 1 month after dose 3 (P < 0.01 for H44/76 and S3032). Against the two SBA-resistant strains, NZ98/254 and S3032, passive protective titers of > or = 1:4 were present in 11 and 42% of sera before immunization, respectively, and these proportions increased to 61 and 94% after immunization (P < 0.001 for each strain). Most of the sera with SBA titers of <1:4 and passive protective activity showed a level of killing in the whole-blood assay (>1 to 2 log(10) decreases in CFU/ml during a 90-min incubation) similar to that of sera with SBA titers of > or = 1:4. In conclusion, passive protective activity was 2.6- to 2.8-fold more frequent than SBA after immunization. The ability of SBA-negative sera to kill Neisseria meningitidis in human blood where fH is bound to the bacteria provides further evidence that SBA titers of > or = 1:4 measured with human complement may underestimate meningococcal immunity.
最近发现补体因子H（fH）与脑膜炎球菌的结合具有人fH特异性。因此，在脑膜炎球菌血症动物模型中测得的被动保护性抗体活性可能高估了对人类的保护作用，因为在没有结合fH的情况下，补体激活不会下调。我们使用非免疫人血建立了脑膜炎球菌血症的体外模型，以测量来自36名接种了研究性脑膜炎球菌多组分重组蛋白疫苗的成年人的储存血清的被动保护活性。免疫前，分别有19%、11%和8%的受试者针对B群菌株H44/76、NZ98/254和S3032的人补体介导的血清杀菌活性（SBA）滴度≥1:4；在第3剂疫苗接种1个月后，这些比例分别增至97%、22%和36%（H44/76和S3032，P<0.01）。针对两种对SBA耐药的菌株NZ98/254和S3032，免疫前分别有11%和42%的血清被动保护滴度≥1:4，免疫后这些比例增至61%和94%（每种菌株P<0.001）。大多数SBA滴度<1:4且具有被动保护活性的血清在全血试验中的杀菌水平（在90分钟孵育期间CFU/ml降低>1至2个对数）与SBA滴度≥1:4的血清相似。总之，免疫后被动保护活性比SBA高2.6至2.8倍。SBA阴性血清在fH与细菌结合的人血中杀死脑膜炎奈瑟菌的能力进一步证明，用人补体测得的SBA滴度≥1:4可能低估了脑膜炎球菌免疫力。
