Ispasanie Emma, Pluschke Gerd, Hodgson Abraham, Sie Ali, MacLennan Calman, Koeberling Oliver
Novartis Vaccines Institute for Global Health, 53100, Siena, Italy ; MRC Centre for Immune Regulation, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK ; Molecular Immunology Department, Swiss Tropical and Public Health Institute, Basel, 4002, Switzerland.
Molecular Immunology Department, Swiss Tropical and Public Health Institute, Basel, 4002, Switzerland ; University of Basel, Basel, 4003, Switzerland.
F1000Res. 2014 Nov 3;3:264. doi: 10.12688/f1000research.3881.1. eCollection 2014.
Neisseria meningitidis is a major cause of bacterial meningitis and a considerable health problem in the 25 countries of the 'African Meningitis Belt' that extends from Senegal in West Africa to Ethiopia in the East. Approximately 80% of cases of meningococcal meningitis in Africa have been caused by strains belonging to capsular serogroup A. After the introduction of a serogroup A conjugate polysaccharide vaccine, MenAfriVac (™), that began in December 2010, the incidence of meningitis due to serogroup A has markedly declined in this region. Currently, serogroup W of N. meningitidis accounts for the majority of cases. Vaccines based on sub-capsular antigens, such as Generalized Modules for Membrane Antigens (GMMA), are under investigation for use in Africa. To analyse the antigenic properties of a serogroup W wave of colonisation and disease, we investigated the molecular diversity of the protein vaccine antigens PorA, Neisserial Adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and factor H binding protein (fHbp) of 31 invasive and carriage serogroup W isolates collected as part of a longitudinal study from Ghana and Burkina Faso between 2003 and 2009. We found that the isolates all expressed fHbp variant 2 ID 22 or 23, differing from each other by only one amino acid, and a single PorA subtype of P1.5,2. Of the isolates, 49% had a functional nhbA gene and 100% had the nadA allele 3, which contained the insertion sequence IS1301 in five isolates. Of the W isolates tested, 41% had high fHbp expression when compared with a reference serogroup B strain, known to be a high expresser of fHbp variant 2. Our results indicate that in this collection of serogroup W isolates, there is limited antigenic diversification over time of vaccine candidate outer membrane proteins (OMP), thus making them promising candidates for inclusion in a protein-based vaccine against meningococcal meningitis for Africa.
脑膜炎奈瑟菌是细菌性脑膜炎的主要病因，在从西非的塞内加尔延伸至东非的埃塞俄比亚的“非洲脑膜炎带”的25个国家中，是一个相当严重的健康问题。非洲约80%的脑膜炎球菌性脑膜炎病例由A群血清型菌株引起。自2010年12月开始引入A群结合多糖疫苗MenAfriVac（™）后，该地区A群引起的脑膜炎发病率显著下降。目前，脑膜炎奈瑟菌W群占大多数病例。基于包膜下抗原的疫苗，如膜抗原通用模块（GMMA），正在非洲进行使用研究。为了分析W群定植和疾病浪潮的抗原特性，我们调查了2003年至2009年间作为纵向研究一部分从加纳和布基纳法索收集的31株侵袭性和携带性W群分离株的蛋白质疫苗抗原PorA、奈瑟菌粘附素A（NadA）、奈瑟菌肝素结合抗原（NHBA）和因子H结合蛋白（fHbp）的分子多样性。我们发现这些分离株均表达fHbp变体2 ID 22或23，彼此之间仅相差一个氨基酸，以及单一的P1.5,2 PorA亚型。在这些分离株中，49%具有功能性nhbA基因，100%具有nadA等位基因3，其中5株含有插入序列IS1301。与已知为fHbp变体2高表达菌株的B群参考菌株相比，所检测的W群分离株中有41%具有高fHbp表达。我们的结果表明，在这组W群分离株中，候选疫苗外膜蛋白（OMP）随时间的抗原多样性有限，因此使其成为有望纳入针对非洲脑膜炎球菌性脑膜炎的基于蛋白质的疫苗的候选者。
