Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters.

Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71-602, FeNP-sG) and Ghead (residues 182-602, FeNP-Ghead) onto E. coli-expressed FeNPs (FeNP-sG and FeNP-Ghead, respectively) through Spycatcher/Spytag technology. Compared with sG and Ghead alone, FeNP-sG and FeNP-Ghead elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-Ghead group. These results further demonstrate that sG possesses greater antigenicity than Ghead and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 µg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.

Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains.

Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.

[Imaging diagnosis of lumbar spinal stenosis].

OBJECTIVE: To investigate value of X-ray, CT and MRI for the diagnosis of lumbar spinal stenosis. METHODS: The data of 130 patients with clinical diagnosis and typical imaging signs of lumbar spinal stenosis were analyzed. The present study included 83 males and 47 females with an average age of 43.5 years (range from 27 to 75 years). CT examination was performed in all patients, routine X-ray examination in 23 patients and routine MRI in 57 patients. RESULTS: The lumbar spinal stenosis showed at L(3,4) plane in 25 patients, L(4,5) in 48 patients and L5S1 in 57 patients. CT showed hyperostosis of lumbar posterior marginal, vertebral lamina, inferior articular process in 46 patients, hypertrophy of superior and inferior articular processsus in 7 patients, calcification or ossification of ligamentum flavum in 13 patients, vertebral body spondylolisthesis in 5 patients, lateral recess stenosis in 24 patients, and intervertebral foramen stenosis in 35 patients. MRI showed intervertebral disk hernia with disc associated with ligamentum flavum hypertrophy in 23 patients, ligamentum flavum symmetrical hypertrophy in 18 patients,extensive multi-segmental ligamentum flavum hypertrophy in 9 patients,and local ligamentum flavum hypertrophy in 7 patients. CONCLUSION: The main cause of secondary lumbar spinal stenosis is degeneration. Traditional X-ray examination has great limitations in diagnosis of lumbar spinal stenosis. CT and MRI have advantages of multi-directional imaging and the high resolution. CT can show well ligament calcification and ossification and other bone change which are showed not well on MRI, so CT is recommended to lumbar spinal stenosis.