Abad R, Biolchi A, Moschioni M, Giuliani M M, Pizza M, Vázquez J A
Reference Laboratory for Meningococci, Institute of Health Carlos III, Majadahonda, Spain
Novartis Vaccines, Siena, Italy.
Clin Vaccine Immunol. 2015 Apr;22(4):357-60. doi: 10.1128/CVI.00669-14. Epub 2015 Jan 28.
A new vaccine (the 4CMenB 4-component protein vaccine [Bexsero], which includes PorA, factor H-binding protein [fHbp], neisserial heparin-binding antigen [NHBA], and Neisseria adhesin A [NadA]) against serogroup B meningococci has recently been approved for use in people older than age 2 months in Europe, Australia, and Canada. Preapproval clinical efficacy studies are not feasible for invasive meningococcal disease because its incidence is low/very low, and the serum bactericidal antibody (SBA) titer (or the human SBA [hSBA] titer when human complement is used in the assay) has been used as a surrogate marker of protection. However, the hSBA assay cannot be used on a large scale, and therefore, a meningococcal antigen typing system (MATS) was developed. MATS combines conventional PorA genotyping with an enzyme-linked immunosorbent assay (ELISA) that quantifies both the expression and the cross-reactivity of antigenic variants. The assay has been used to evaluate the potential of the 4CMenB meningococcal group B vaccine to cover group B strains in several countries. Some recent data suggest that MATS is a conservative predictor of strain coverage. We used pooled sera from adolescents and infants to test by the hSBA assay 10 meningococcal group B strains isolated in Spain that were negative for the 3 antigens (n = 9) or that had very low levels of the 3 antigens (n = 1) by MATS. We found that all strains were killed by sera from adolescents and that 5 of the 10 strains were also killed, although at a low titer, by sera from infants. Our data confirm that MATS underestimates vaccine coverage.
一种针对B群脑膜炎球菌的新型疫苗(4CMenB四组分蛋白疫苗[Bexsero],包括PorA、因子H结合蛋白[fHbp]、奈瑟菌肝素结合抗原[NHBA]和奈瑟菌粘附素A[NadA])最近已在欧洲、澳大利亚和加拿大被批准用于2个月以上的人群。由于侵袭性脑膜炎球菌病的发病率低/极低,因此对其进行批准前的临床疗效研究不可行,血清杀菌抗体(SBA)滴度(或在检测中使用人补体时的人SBA[hSBA]滴度)已被用作保护的替代标志物。然而,hSBA检测无法大规模使用,因此,开发了一种脑膜炎球菌抗原分型系统(MATS)。MATS将传统的PorA基因分型与一种酶联免疫吸附测定(ELISA)相结合,该测定可量化抗原变体的表达和交叉反应性。该测定已被用于评估4CMenB B群脑膜炎球菌疫苗在几个国家覆盖B群菌株的潜力。最近的一些数据表明,MATS是菌株覆盖率的保守预测指标。我们使用青少年和婴儿的混合血清,通过hSBA检测对在西班牙分离的10株B群脑膜炎球菌菌株进行检测,这些菌株通过MATS检测对3种抗原呈阴性(n = 9)或3种抗原水平极低(n = 1)。我们发现,所有菌株都被青少年的血清杀死,10株菌株中的5株也被婴儿的血清杀死,尽管滴度较低。我们的数据证实,MATS低估了疫苗覆盖率。