Vermont C L, van Dijken H H, Kuipers A J, van Limpt C J P, Keijzers W C M, van der Ende A, de Groot R, van Alphen L, van den Dobbelsteen G P J M
Laboratory for Vaccine Research, Netherlands Vaccine Institute (NVI), PO Box 457, 3720 AL Bilthoven, The Netherlands.
Infect Immun. 2003 Apr;71(4):1650-5. doi: 10.1128/IAI.71.4.1650-1655.2003.
The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (> or =4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were cross-reactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.
通过血清杀菌试验（SBA）研究了单价P1.7 - 2,4（MonoMen）和/或六价（HexaMen）B群脑膜炎球菌外膜囊泡疫苗（OMV）在幼儿和学龄儿童中诱导的PorA特异性抗体的交叉反应性。首先，将同基因疫苗菌株和PorA相同的患者分离株作为SBA的靶标进行比较，以确保疫苗菌株能代表患者分离株。接种HexaMen后，SBA中针对P1.5 - 2,10和P1.5 - 1,2 - 2亚型患者分离株的几何平均滴度（GMT）通常低于针对相同亚型疫苗菌株的GMT，不过疫苗应答者的百分比（接种后SBA增加≥4倍）未受影响。使用各种P1.7 - 2,4患者分离株时，GMT以及疫苗应答者数量均高于P1.7 - 2,4疫苗菌株，这表明使用P1.7 - 2,4疫苗菌株可能低估了HexaMen中该亚型的免疫原性。其次，使用几种与疫苗亚型不同的患者分离株研究了MonoMen和HexaMen诱导的抗体的交叉反应性，这些分离株具有一个可变区（VR）的微小抗原变异、具有完全不同的VR或具有不同的VR组合。MonoMen诱导的P1.4特异性抗体与P1.4变体P1.4 - 1和P1.4 - 3具有交叉反应性。HexaMen诱导了更广泛的交叉反应性抗体应答，针对各种患者分离株，这些分离株的一个VR与疫苗亚型相同或包含在HexaMen中的VR组合相同。接种后SBA增加四倍所衡量的针对这些菌株的交叉反应性，根据测试菌株的亚型不同，范围为23%至92%，且针对VR1和VR2。HexaMen诱导的疫苗接种者血清对抗原变异体的扩展交叉反应性对B群脑膜炎球菌OMV疫苗的覆盖率具有重要的有利影响。
