中文摘要：人类乳头瘤病毒(HPV)是一种全球流行的性传播病毒，引发大多数宫颈癌。HPV疫苗接种率尚不理想，部分原因是需要多次接种，导致缺乏依从性和不完全保护。为了解决目前HPV疫苗的缺点，本研究采用一种可扩展的制造工艺以制备可植入的聚合物-蛋白质混合物，用作单次给药缓释剂。将HPV16衣壳蛋白L2的多肽表位与源自噬菌体Qβ的病毒样颗粒结合，增强其免疫原性。用台式熔融处理系统将HPV-Qβ粒子封装到聚乳酸-羟基乙酸（PLGA）植入物中。在高温熔融过程中，植入物促进HPV-Qβ粒子的缓慢和持续释放，而不丧失纳米粒子的完整性。接种这种植入物的小鼠产生的IgG滴度与传统的可溶性注射相当，并在假病毒中和试验中起到保护作用。HPV-Qβ植入物提供了一个新的疫苗接种平台，而熔融处理功能多样，该项技术可为任何几何形状的大规模高端产品提供机会。尤其在发展中国家，微针贴片可以在没有专业医护人员的情况下进行自我给药。Qβ技术适应性很强，可以生产多种毒株或病毒的候选疫苗及其输送装置。
外文摘要：Human papillomavirus (HPV) is a globally prevalent sexually-transmitted pathogen, responsible for most cases of cervical cancer. HPV vaccination rates remain suboptimal, partly due to the need for multiple doses, leading to a lack of compliance and incomplete protection. To address the drawbacks of current HPV vaccines, we used a scalable manufacturing process to prepare implantable polymer-protein blends for single-administration with sustained delivery. Peptide epitopes from HPV16 capsid protein L2 were conjugated to the virus-like particles derived from bacteriophage Q beta, to enhance their immunogenicity. The HPV-Q beta particles were then encapsulated into poly(lactic-co-glycolic acid) (PLGA) implants, using a benchtop melt-processing system. The implants facilitated the slow and sustained release of HPV-Q beta particles without the loss of nanoparticle integrity, during high temperature melt processing. Mice vaccinated with the implants generated IgG titers comparable to the traditional soluble injections and achieved protection in a pseudovirus neutralization assay.
HPV-Q beta implants offer a new vaccination platform; because the melt-processing is so versatile, the technology offers the opportunity for massive upscale into any geometric form factor. Notably, microneedle patches would allow for self-administration in the absence of a healthcare professional, within the developing world. The Q beta technology is highly adaptable, allowing the production of vaccine candidates and their delivery devices for multiple strains or types of viruses.
外文关键词：HPV vaccine candidate；L2 protein；Qβ；virus-like particles (VLPs)；PLGA implants；vaccine delivery device；hot melt extrusion
作者：Shao, S；Ortega-Rivera, OA；Ray, S；Pokorski, JK；Steinmetz, NF
作者单位：Univ Calif San Diego
期刊名称：VACCINES
期刊影响因子：5.699
出版年份：2021
出版刊次：1
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