Vermont Clementien L, van Dijken Harry H, de Groot Ronald, van den Dobbelsteen Germie P J M
Laboratory for Vaccine Research, Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands.
Pediatr Res. 2005 Jul;58(1):149-52. doi: 10.1203/01.PDR.0000156372.13569.08. Epub 2005 Mar 17.
Porin A (PorA), which determines the serosubtype of Neisseria meningitidis, is the main antigen of a candidate vaccine against serogroup B meningococci, which has been shown to induce high-avidity antibodies in children. We characterized the immune response of children after convalescing from meningococcal infection with a serosubtype P1.7-2,4 strain. Acute- and convalescent-phase sera of 21 children with meningococcal septic shock caused by strains with PorA subtype P1.7-2,4 were collected. The serum bactericidal antibody titers, IgG isotype distribution, and antibody avidity were measured. We determined whether the differences in avidity of anti-outer membrane vesicle antibodies were PorA specific. Serum bactericidal activity against H44/76 P1.7-2,4 was <4 in all convalescent sera. The IgG isotype distribution of the convalescent sera was dominated by IgG(1), followed by IgG(3), whereas no IgG(2) or IgG(4) was found. The geometric mean avidity index (GMAI) of convalescent sera measured against a strain with the identical subtype as the infective isolate was significantly higher than that against a strain with a heterologous PorA subtype or a PorA-negative mutant strain (57 versus 35 and 23%, respectively; p = 0.005 and p < 0.001). Geometric mean avidity titers were highest for P1.7-2,4, corresponding with the highest GMAI. The GMAI after invasive meningococcal disease was lower than after vaccination of healthy toddlers with a monovalent P1.7-2,4 outer membrane vesicle vaccine.
决定脑膜炎奈瑟菌血清亚型的孔蛋白A(PorA)是B群脑膜炎球菌候选疫苗的主要抗原,已证明该疫苗可在儿童中诱导高亲和力抗体。我们对感染血清亚型为P1.7-2,4菌株的脑膜炎球菌后康复的儿童的免疫反应进行了表征。收集了21例由PorA亚型为P1.7-2,4的菌株引起的脑膜炎球菌感染性休克儿童的急性期和恢复期血清。测量了血清杀菌抗体滴度、IgG同种型分布和抗体亲和力。我们确定了抗外膜囊泡抗体亲和力的差异是否具有PorA特异性。所有恢复期血清中针对H44/76 P1.7-2,4的血清杀菌活性均<4。恢复期血清的IgG同种型分布以IgG(1)为主,其次是IgG(3),未发现IgG(2)或IgG(4)。针对与感染分离株亚型相同的菌株测量的恢复期血清的几何平均亲和力指数(GMAI)显著高于针对异源PorA亚型菌株或PorA阴性突变株的GMAI(分别为57%对35%和23%;p = 0.005和p < 0.001)。P1.7-2,4的几何平均亲和力滴度最高,与最高的GMAI相对应。侵袭性脑膜炎球菌病后的GMAI低于用单价P1.7-2,4外膜囊泡疫苗对健康幼儿进行疫苗接种后的GMAI。