Moon Seo Young, Flores Rochelle A, Yim Min Su, Lim Heeji, Kim Seungyeon, Lee Seung Yun, Lee Yoo-Kyoung, Kim Jae-Ouk, Park Hyejin, Bae Seong Eun, Ouh In-Ohk, Kim Woo H
Division of Vaccine Development Coordination, Center for Vaccine Research National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Chungcheongbuk-do, Republic of Korea.
College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Gyeongsangnam-do, Republic of Korea.
Vaccines (Basel). 2024 Aug 31;12(9):999. doi: 10.3390/vaccines12090999.
Nipah virus (NiV), of the Paramyxoviridae family, causes highly fatal infections in humans and is associated with severe neurological and respiratory diseases. Currently, no commercial vaccine is available for human use. Here, eight structure-based mammalian-expressed recombinant proteins harboring the NiV surface proteins, fusion glycoprotein (F), and the major attachment glycoprotein (G) were produced. Specifically, prefusion NiV-F and/or NiV-G glycoproteins expressed in monomeric, multimeric (trimeric F and tetra G), or chimeric forms were evaluated for their properties as sub-unit vaccine candidates. The antigenicity of the recombinant NiV glycoproteins was evaluated in intramuscularly immunized mice, and the antibodies in serum were assessed. Predictably, all homologous immunizations exhibited immunogenicity, and neutralizing antibodies to VSV-luciferase-based pseudovirus expressing NiV-GF glycoproteins were found in all groups. Comparatively, neutralizing antibodies were highest in vaccines designed in their multimeric structures and administered as bivalent (GMYtet + GBDtet) and trivalent (Ftri + GMYtet + GBDtet). Additionally, while all adjuvants were able to elicit an immunogenic response in vaccinated groups, bivalent (GMYtet + GBDtet) and trivalent (Ftri + GMYtet + GBDtet) induced more potent neutralizing antibodies when administered with oil-in-water nano-emulsion adjuvant, AddaS03. For all experiments, the bivalent GMYtet + GBDtet was the most immunogenic vaccine candidate. Results from this study highlight the potential use of these mammalian-expressed recombinant NiV as vaccine candidates, deserving further exploration.
尼帕病毒（NiV）属于副粘病毒科，可引发人类的高致死性感染，并与严重的神经和呼吸系统疾病相关。目前，尚无用于人类的商用疫苗。在此，制备了八种基于结构的哺乳动物表达的重组蛋白，这些蛋白含有NiV表面蛋白、融合糖蛋白（F）和主要附着糖蛋白（G）。具体而言，对以单体、多聚体（三聚体F和四聚体G）或嵌合形式表达的预融合NiV-F和/或NiV-G糖蛋白作为亚单位疫苗候选物的特性进行了评估。在肌肉注射免疫的小鼠中评估了重组NiV糖蛋白的抗原性，并对血清中的抗体进行了评估。不出所料，所有同源免疫均表现出免疫原性，并且在所有组中均发现了针对表达NiV-GF糖蛋白的基于VSV-荧光素酶的假病毒的中和抗体。相比之下，以多聚体结构设计并作为二价（GMYtet + GBDtet）和三价（Ftri + GMYtet + GBDtet）给药的疫苗中的中和抗体最高。此外，虽然所有佐剂都能够在接种组中引发免疫反应，但二价（GMYtet + GBDtet）和三价（Ftri + GMYtet + GBDtet）与水包油纳米乳液佐剂AddaS03一起给药时诱导产生更有效的中和抗体。对于所有实验，二价GMYtet + GBDtet是最具免疫原性的疫苗候选物。这项研究的结果突出了这些哺乳动物表达的重组NiV作为疫苗候选物的潜在用途，值得进一步探索。
