Lucidarme Jay, Gilchrist Stefanie, Newbold Lynne S, Gray Stephen J, Kaczmarski Edward B, Richardson Lynne, Bennett Julia S, Maiden Martin C J, Findlow Jamie, Borrow Ray
Vaccine Evaluation Unit, Public Health England, Manchester, United Kingdom.
Clin Vaccine Immunol. 2013 Sep;20(9):1360-9. doi: 10.1128/CVI.00090-13. Epub 2013 Jun 26.
The poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.
B群脑膜炎球菌(MenB)荚膜的免疫原性较差,这促使人们研发针对荚膜下抗原的疫苗,特别是免疫显性且多样的外膜孔蛋白PorA。这些疫苗在很大程度上具有菌株特异性;然而,它们对许多工业化国家中观察到的多种与MenB相关的疾病提供的保护有限。为了扩大其保护范围,多组分疫苗(4CMenB)将含PorA的外膜囊泡(OMV)与相对保守的重组蛋白成分相结合,包括因子H结合蛋白(fHbp)、奈瑟菌粘附素A(NadA)和奈瑟菌肝素结合抗原(NHBA)。PorA的表达是脑膜炎球菌(脑膜炎奈瑟菌)所特有的;然而,许多荚膜下抗原与也栖息于鼻咽部的奈瑟菌属非致病成员共有。这些生物体可能引发针对脑膜炎球菌的交叉保护性免疫和/或占据原本可能容纳病原体的生态位。通过确定常见儿童共生菌乳酸奈瑟菌不同成员中主要4CMenB抗原的基因分布,研究了4CMenB反应影响此类物种的可能性(反之亦然)。所有分离株都含有nhba,但缺乏fhbp和nadA。nhba等位基因主要与来自同一广泛地理区域的侵袭性MenB分离株代表性面板中观察到的等位基因不同,但密切相关。对于构成4CMenB OMV主要部分的免疫原性分型抗原FetA,我们也有类似的发现。因此,4CMenB疫苗反应可能会受到共生奈瑟菌鼻咽部携带情况的影响,反之亦然。这突出了一个在常规实施该疫苗时需要进一步研究和监测的领域。