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聚合物配方的自扩增RNA疫苗对雪貂的流感病毒感染具有部分保护作用。

Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets.

作者信息

McKay P F, Zhou J, Frise R, Blakney A K, Bouton C R, Wang Z, Hu K, Samnuan K, Brown J C, Kugathasan R, Yeow J, Stevens M M, Barclay W S, Tregoning J S, Shattock R J

机构信息

Department of Infectious Disease, Imperial College London, London W2 1PG, UK.

Departments of Materials and Bioengineering, Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.

出版信息

Oxf Open Immunol. 2022 Jun 27;3(1):iqac004. doi: 10.1093/oxfimm/iqac004. eCollection 2022.

Abstract

COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.

摘要

新冠病毒已证明RNA疫苗作为大流行应对工具包一部分的强大作用。另一种具有大流行潜力的病毒是流感病毒。在未来流感大流行之前进一步开发RNA疫苗将节省时间并挽救生命。由于RNA疫苗需要进行制剂处理以进入细胞并诱导抗原表达,本研究的目的是调查一种最近开发的可生物还原的阳离子聚合物pABOL对在小鼠和雪貂中递送用于季节性流感病毒的自扩增RNA(saRNA)疫苗的影响。用表达来自H1N1或H3N2流感病毒血凝素(HA)的pABOL制剂saRNA疫苗以初免-加强方案免疫小鼠和雪貂。免疫后在血清中测量结合抗体和功能性抗体反应。然后通过鼻内接种或在接触传播模型中直接用匹配的流感病毒攻击动物。虽然在小鼠中具有高度免疫原性,但pABOL制剂的saRNA在雪貂中产生了不同的反应。对疫苗产生较高水平流感病毒特异性中和抗体反应的动物对流感病毒感染的保护作用更强。pABOL制剂的saRNA在雪貂中具有免疫原性,但需要进一步优化RNA疫苗制剂和构建体,以提高对疫苗抗体反应的质量和数量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f30d/9914471/60ed7a195704/iqac004f1.jpg

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