Vezzani Giacomo, Viviani Viola, Audagnotto Martina, Rossi Alessandro, Cinelli Paolo, Pacchiani Nicola, Limongi Chiara, Santini Laura, Giusti Fabiola, Tomei Sara, Torricelli Giulia, Faenzi Elisa, Sammicheli Chiara, Tavarini Simona, Efron Adriana, Biolchi Alessia, Finco Oretta, Delany Isabel, Frigimelica Elisabetta
GSK Vaccines, Siena, Italy.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy.
Front Immunol. 2025 Apr 16;16:1565862. doi: 10.3389/fimmu.2025.1565862. eCollection 2025.
The 4CMenB vaccine licensed against serogroup B Neisseria meningitidis (MenB) contains three recombinant proteins and Outer Membrane Vesicles (OMV) from a New Zealand epidemic strain. The protective response mediated on differentmeningococcal strains has been historically ascribed to one of the four main vaccine antigens fHbp, NHBA, NadA, and PorA nominated as the immunodominant antigen of the OMV component. It is however accepted that the extensive cross-protection observed after vaccination may be attributed to other proteins in the OMV. Here we interrogate the B cell responses elicited in humans to the OMV component after 4CMenB vaccination to elucidate the contribution of additional OMV antigens to meningococcal cross-protection.
Following the isolation of plasmablasts from vaccinees, the OMV-specific human monoclonal antibodies (HumAbs) were recombinantly expressed and characterized for their binding and functional activity on a panel of MenB strains. Their target specificity was assessed through a tailor-made protein array and Western blot.
We found that 18 HumAbs showing bactericidal activity were PorB-specific, 1 was LOS-specific and 4 functional HumAbs remain with unknown targets. We identified three functional classes within the PorB HumAbs, through binding and in silico docking experiments, likely to be elicited from distinct epitopes on PorB and highlighting this antigen as a multi-epitope immunogenic OMV component responsible for distinct cross-protection across multiple MenB strains. Interestingly three of the PorB HumAbs and the LOS-specific HumAb showed bactericidal activity also against gonococcus.
We identified PorB and LOS as antigens on the OMV that may be implicated in the real-world observations of moderate protection against gonorrhea infection after OMV-based vaccinations.
已获许可的针对B群脑膜炎奈瑟菌（MenB）的4CMenB疫苗包含三种重组蛋白和来自一株新西兰流行菌株的外膜囊泡（OMV）。历史上，针对不同脑膜炎球菌菌株介导的保护性反应归因于四种主要疫苗抗原之一，即被指定为OMV组分免疫显性抗原的fHbp、NHBA、NadA和PorA。然而，人们认为接种疫苗后观察到的广泛交叉保护可能归因于OMV中的其他蛋白。在此，我们探究了4CMenB疫苗接种后人体对OMV组分引发的B细胞反应，以阐明其他OMV抗原对脑膜炎球菌交叉保护的贡献。
从疫苗接种者中分离出浆母细胞后，重组表达OMV特异性人单克隆抗体（HumAbs），并对其在一组MenB菌株上的结合和功能活性进行表征。通过特制的蛋白质阵列和蛋白质印迹评估其靶标特异性。
我们发现18种具有杀菌活性的HumAbs是PorB特异性的，1种是LOS特异性的，4种具有功能的HumAbs的靶标仍未知。通过结合和计算机对接实验，我们在PorB HumAbs中确定了三个功能类别，它们可能由PorB上不同的表位引发，这突出了该抗原作为一种多表位免疫原性OMV组分，负责对多种MenB菌株的不同交叉保护。有趣的是，三种PorB HumAbs和LOS特异性HumAb对淋球菌也具有杀菌活性。
我们确定PorB和LOS是OMV上的抗原，它们可能与基于OMV的疫苗接种后对淋病感染具有中度保护作用的实际观察结果有关。
