Caliciviruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
Viruses. 2019 May 10;11(5):432. doi: 10.3390/v11050432.
Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis. Vaccine design has been confounded by the antigenic diversity of these viruses and a limited understanding of protective immunity. We reviewed 77 articles published since 1988 describing the isolation, function, and mapping of 307 unique monoclonal antibodies directed against B cell epitopes of human and murine noroviruses representing diverse Genogroups (G). Of these antibodies, 91, 153, 21, and 42 were reported as GI-specific, GII-specific, MNV GV-specific, and G cross-reactive, respectively. Our goal was to reconstruct the antigenic topology of noroviruses in relationship to mapped epitopes with potential for therapeutic use or inclusion in universal vaccines. Furthermore, we reviewed seven published studies of norovirus T cell epitopes that identified 18 unique peptide sequences with CD4- or CD8-stimulating activity. Both the protruding (P) and shell (S) domains of the major capsid protein VP1 contained B and T cell epitopes, with the majority of neutralizing and HBGA-blocking B cell epitopes mapping in or proximal to the surface-exposed P2 region of the P domain. The majority of broadly reactive B and T cell epitopes mapped to the S and P1 arm of the P domain. Taken together, this atlas of mapped B and T cell epitopes offers insight into the promises and challenges of designing universal vaccines and immunotherapy for the noroviruses.
人类诺如病毒(HuNoV)是急性非细菌性胃肠炎的主要原因。这些病毒的抗原多样性以及对保护性免疫的有限了解,使得疫苗设计变得复杂。我们回顾了自 1988 年以来发表的 77 篇描述针对人类和鼠诺如病毒 B 细胞表位的分离、功能和定位的文章,这些病毒代表了不同的基因群(G)。在这些抗体中,91、153、21 和 42 分别被报道为 GI 特异性、GII 特异性、MNV GV 特异性和 G 交叉反应性。我们的目标是重建诺如病毒的抗原拓扑结构,与潜在用于治疗或包含在通用疫苗中的映射表位相关。此外,我们还回顾了七项已发表的诺如病毒 T 细胞表位研究,这些研究确定了 18 个具有 CD4 或 CD8 刺激活性的独特肽序列。主要衣壳蛋白 VP1 的突出(P)和壳(S)结构域均包含 B 和 T 细胞表位,大多数中和和 HBGA 阻断 B 细胞表位位于 P 域表面暴露的 P2 区域内或附近。大多数广泛反应的 B 和 T 细胞表位定位于 P 域的 S 和 P1 臂。总的来说,这个映射的 B 和 T 细胞表位图谱为设计通用疫苗和诺如病毒免疫疗法提供了深入了解其前景和挑战。