Specificity of Bactericidal Antibody Response to Serogroup B Meningococcal Strains in Brazilian Children after Immunization with an Outer Membrane Vaccine

Pre- and postvaccination serum samples from 77 children aged 2 to 6 years, who received the Cuban BC vaccine (B:4:P1.15), were analyzed for bactericidal antibodies against a local B:4:P1.15 strain (N44/89). Sera from 16 individuals with bactericidal antibodies against the B:4:P1.15 strain were tested against 23 Brazilian isolates. These include B:4 strains of distinct serosubtypes: P1.15, P1.7,1, P1.3, P1.9, P1.nt, and a B:8,19,23:P1.16 strain. A Cuban B:4:P1.15 strain (Cu385/83) was also included in the study. The specificities of bactericidal antibodies were analyzed by using mutant strains lacking a class 1 protein (PorA protein) or a class 5 protein or both. The results indicated that PorA and class 5 proteins are the main targets recognized by the bactericidal antibodies of vaccinees. Nonetheless, a complex pattern of recognition by bactericidal antibodies was found, and vaccinees were grouped according to antibody specificity. Antibodies from some individuals recognized PorA of serosubtype P1.15. However, antibodies from these individuals could not kill all P1.15 strains tested. Antibodies from a second group recognized both PorA and class 5 proteins, and antibodies from a third group recognized an as yet unidentified target antigen. The results demonstrate the importance of determining the fine epitope specificity of bactericidal antibodies to improve the existing vaccines against B meningococci.

本研究对77名2~6岁接种古巴BC疫苗（B:4:P1.15）的儿童的接种前、后血清样本进行分析，检测其针对本地B:4:P1.15菌株（N44/89）的杀菌抗体。选取16名针对B:4:P1.15菌株具有杀菌抗体的个体的血清，对23株巴西分离株进行检测，受试分离株涵盖不同血清亚型的B:4菌株：P1.15、P1.7,1、P1.3、P1.9、P1.nt，以及1株B:8,19,23:P1.16菌株；本研究同时纳入了1株古巴B:4:P1.15菌株（Cu385/83）。研究通过使用缺失1类蛋白（PorA蛋白）、5类蛋白或同时缺失两类蛋白的突变菌株，分析杀菌抗体的特异性。结果显示，PorA蛋白与5类蛋白是疫苗接种者体内杀菌抗体识别的主要靶标。然而，本研究发现杀菌抗体的识别模式较为复杂，遂根据抗体特异性将疫苗接种者分为三组：部分个体的抗体可识别血清亚型P1.15的PorA蛋白，但该群体的抗体无法杀灭所有受试的P1.15菌株；第二组个体的抗体可同时识别PorA蛋白与5类蛋白；第三组个体的抗体则识别一种尚未被鉴定的靶抗原。本研究结果证实，明确杀菌抗体的精细表位特异性，对于优化现有B群脑膜炎球菌疫苗具有重要意义。