Roe Shea K, Zhu Tianmou, Slepenkin Anatoli, Berges Aym, Fairman Jeff, de la Maza Luis M, Massari Paola
Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.
Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA.
Vaccines (Basel). 2024 Jul 18;12(7):789. doi: 10.3390/vaccines12070789.
() is the most common cause of bacterial sexually transmitted infections (STIs) worldwide. infections are often asymptomatic in women, leading to severe reproductive tract sequelae. Development of a vaccine against is crucial. The major outer membrane protein (MOMP) is a prime vaccine antigen candidate, and it can elicit both neutralizing antibodies and protective CD4+ T cell responses. We have previously designed chimeric antigens composed of immunogenic variable regions (VDs) and conserved regions (CDs) of MOMP from () expressed into a carrier protein (PorB), and we have shown that these were protective in a mouse model of respiratory infection. Here, we generated corresponding constructs based on MOMP from serovar F. Preliminary structure analysis of the three antigens, PorB/VD1-3, PorB/VD1-4 and PorB/VD1-2-4, showed that they retained structure features consistent with those of PorB. The antigens induced robust humoral and cellular responses in mice with different genetic backgrounds. The antibodies were cross-reactive against but only anti-PorB/VD1-4 and anti-PorB/VD1-2-4 IgG antibodies were neutralizing, likely due to the antigen specificity. The cellular responses included proliferation in vitro and production of IFN-γ by splenocytes following re-stimulation. Our results support further investigation of the PorB/VD antigens as potential protective candidates for a subunit vaccine.
（某病原体）是全球细菌性性传播感染（STIs）最常见的病因。该病原体感染在女性中通常无症状，会导致严重的生殖道后遗症。研发针对该病原体的疫苗至关重要。该病原体主要外膜蛋白（MOMP）是主要的疫苗抗原候选物，它能引发中和抗体和保护性CD4 + T细胞反应。我们之前设计了嵌合抗原，其由来自（某病原体）的MOMP的免疫原性可变区（VDs）和保守区（CDs）组成，并表达于载体蛋白（PorB）中，且已表明这些嵌合抗原在该病原体呼吸道感染的小鼠模型中具有保护作用。在此，我们基于血清型F的该病原体MOMP生成了相应构建体。对三种抗原PorB/VD1 - 3、PorB/VD1 - 4和PorB/VD1 - 2 - 4的初步结构分析表明，它们保留了与PorB一致的结构特征。这些抗原在具有不同遗传背景的小鼠中诱导了强烈的体液和细胞反应。这些抗体对该病原体具有交叉反应性，但只有抗PorB/VD1 - 4和抗PorB/VD1 - 2 - 4 IgG抗体具有中和作用，这可能归因于抗原特异性。细胞反应包括体外增殖以及再次刺激后脾细胞产生IFN - γ。我们的结果支持进一步研究PorB/VD抗原作为该病原体亚单位疫苗的潜在保护性候选物。
