Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Front Immunol. 2020 Jan 9;10:2966. doi: 10.3389/fimmu.2019.02966. eCollection 2019.
infections remain a challenging health issue, causing significant morbidity and mortality worldwide. Current vaccines against typhoid fever display moderate efficacy whilst no licensed vaccines are available for paratyphoid fever or invasive non-typhoidal salmonellosis. Therefore, there is an urgent need to develop high efficacy broad-spectrum vaccines that can protect against typhoidal and non-typhoidal . The outer membrane porins OmpC and OmpF, have been shown to be highly immunogenic antigens, efficiently eliciting protective antibody, and cellular immunity. Furthermore, enterobacterial porins, particularly the OmpC, have a high degree of homology in terms of sequence and structure, thus making them a suitable vaccine candidate. However, the degree of the amino acid conservation of OmpC among typhoidal and non-typhoidal serovars is currently unknown. Here we used a bioinformatical analysis to classify the typhoidal and non-typhoidal OmpC amino acid sequences into different clades independently of their serological classification. Further, our analysis determined that the porin OmpC contains various amino acid sequences that are highly conserved among both typhoidal and non-typhoidal serovars. Critically, some of these highly conserved sequences were located in the transmembrane β-sheet within the porin β-barrel and have immunogenic potential for binding to MHC-II molecules, making them suitable candidates for a broad-spectrum vaccine. Collectively, these findings suggest that these highly conserved sequences may be used for the rational design of an effective broad-spectrum vaccine against .
感染仍然是一个具有挑战性的健康问题，在全球范围内导致了大量的发病率和死亡率。目前针对伤寒的疫苗显示出中等疗效，而副伤寒或侵袭性非伤寒沙门氏菌病则没有许可的疫苗。因此，迫切需要开发高效广谱疫苗，以预防伤寒和非伤寒。外膜孔蛋白 OmpC 和 OmpF 已被证明是高度免疫原性抗原，能有效地引起保护性抗体和细胞免疫。此外，肠杆菌孔蛋白，特别是 OmpC，在序列和结构上具有高度的同源性，因此成为一种合适的疫苗候选物。然而，目前尚不清楚 OmpC 在伤寒和非伤寒血清型之间的氨基酸保守程度。在这里，我们使用生物信息学分析将伤寒和非伤寒血清型的 OmpC 氨基酸序列独立于其血清学分型分类为不同的进化枝。此外，我们的分析确定，该孔蛋白 OmpC 包含各种在伤寒和非伤寒血清型中高度保守的氨基酸序列。重要的是，这些高度保守的序列中的一些位于孔蛋白 β-桶内的跨膜β-折叠中，具有与 MHC-II 分子结合的免疫原性潜力，使它们成为广谱疫苗的合适候选物。总的来说，这些发现表明这些高度保守的序列可能被用于合理设计针对的有效广谱疫苗。
