关键词: Nipah virus attachment glycoproteins (G) cross-reactivity divalent vaccine immune responses nanoparticle vaccine

Mesh : Animals Nipah Virus / immunology Henipavirus Infections / prevention & control immunology Ferritins / immunology Mesocricetus Antibodies, Viral / immunology blood Antibodies, Neutralizing / immunology blood Nanoparticles Viral Vaccines / immunology administration & dosage Cricetinae Vaccines, Virus-Like Particle / immunology administration & dosage Female Humans Nanovaccines

来  源:   DOI:10.3389/fimmu.2024.1387811   PDF(Pubmed)

Abstract:
The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.
摘要:
尼帕病毒(NiV)一种高度致命的蝙蝠传播的副粘病毒,由于特定地区的反复爆发,构成了重大威胁,引起严重的呼吸系统和神经系统疾病,发病率高。两种不同的菌株,NiV-马来西亚(NiV-M)和NiV-孟加拉国(NiV-B),导致不同地理区域的疫情爆发。目前,没有商业许可的疫苗或药物可用于预防或治疗。为了应对这种针对NiV和相关亨尼帕病毒感染的保护的迫切需求,我们开发了一种新型的同型病毒样纳米颗粒(VLP)疫苗,共同展示来自两种菌株的NiV附着糖蛋白(G),利用铁蛋白蛋白的自组装特性。与NiVG亚单位疫苗相比,我们的纳米颗粒疫苗在叙利亚仓鼠中引发了显著更高水平的中和抗体,并提供了针对NiV感染致死性攻击的完全保护.值得注意的是,纳米颗粒疫苗刺激了抗体的产生,这些抗体表现出与同源或异源乙型肝炎病毒的优异交叉反应性。这些发现强调了基于铁蛋白的纳米颗粒疫苗在提供广谱和长期保护以抵抗NiV和新出现的人畜共患乙型肝炎病毒挑战方面的潜在效用。
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