Department for Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
Viruses. 2022 Mar 3;14(3):521. doi: 10.3390/v14030521.
Negative-stranded RNA viruses (NSVs) are important human pathogens, including emerging and reemerging viruses that cause respiratory, hemorrhagic and other severe illnesses. Vaccine design traditionally relies on the viral surface glycoproteins. However, surface glycoproteins rarely elicit effective long-term immunity due to high variability. Therefore, an alternative approach is to include conserved structural proteins such as nucleoprotein (NP). NP is engaged in myriad processes in the viral life cycle: coating and protection of viral RNA, regulation of transcription/replication processes and induction of immunosuppression of the host. A broad heterosubtypic T-cellular protection was ascribed very early to this protein. In contrast, the understanding of the humoral immunity to NP is very limited in spite of the high titer of non-neutralizing NP-specific antibodies raised upon natural infection or immunization. In this review, the data with important implications for the understanding of the role of NP in the immune response to human NSVs are revisited. Major implications of the elicited T-cell immune responses to NP are evaluated, and the possible multiple mechanisms of the neglected humoral response to NP are discussed. The intention of this review is to remind that NP is a very promising target for the development of future vaccines.
负链 RNA 病毒（NSVs）是重要的人类病原体，包括新兴和重现的病毒，可引起呼吸道、出血性和其他严重疾病。疫苗设计传统上依赖于病毒表面糖蛋白。然而，由于高度变异性，表面糖蛋白很少引起有效的长期免疫。因此，另一种方法是包括保守的结构蛋白，如核蛋白（NP）。NP 参与病毒生命周期中的众多过程：包裹和保护病毒 RNA、调节转录/复制过程以及诱导宿主免疫抑制。这种蛋白质很早就被归因于广泛的异源 T 细胞保护。相比之下，尽管在自然感染或免疫接种后会产生高滴度的非中和性 NP 特异性抗体，但对 NP 体液免疫的理解非常有限。在这篇综述中，重新回顾了对理解 NP 在人类 NSV 免疫反应中的作用具有重要意义的数据。评估了针对 NP 的 T 细胞免疫反应的主要影响，并讨论了被忽视的针对 NP 的体液反应的可能多种机制。撰写本文的目的是提醒大家，NP 是开发未来疫苗的一个非常有前途的目标。
