Shao Shuai, A Ortega-Rivera Oscar, Ray Sayoni, K Pokorski Jonathan, F Steinmetz Nicole
Department of NanoEngineering, University of California San Diego, La Jolla, CA 92093, USA.
Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, CA 92093, USA.
Vaccines (Basel). 2021 Jan 19;9(1):66. doi: 10.3390/vaccines9010066.
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 Qβ, to enhance their immunogenicity. The HPV-Qβ 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-Qβ 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-Qβ 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 Qβ technology is highly adaptable, allowing the production of vaccine candidates and their delivery devices for multiple strains or types of viruses.
人乳头瘤病毒（HPV）是一种全球流行的性传播病原体，是大多数宫颈癌病例的病因。HPV疫苗接种率仍未达到最佳水平，部分原因是需要多剂接种，导致依从性差和保护不完整。为了解决当前HPV疫苗的缺点，我们采用了一种可扩展的制造工艺来制备可植入的聚合物-蛋白质混合物，用于单次给药并实现持续释放。将来自HPV16衣壳蛋白L2的肽表位与源自噬菌体Qβ的病毒样颗粒偶联，以增强其免疫原性。然后使用台式熔融加工系统将HPV-Qβ颗粒封装到聚乳酸-乙醇酸共聚物（PLGA）植入物中。在高温熔融加工过程中，植入物促进了HPV-Qβ颗粒的缓慢持续释放，而不会损失纳米颗粒的完整性。用植入物接种的小鼠产生的IgG滴度与传统的可溶性注射相当，并在假病毒中和试验中实现了保护。HPV-Qβ植入物提供了一个新的疫苗接种平台；由于熔融加工非常通用，该技术为大规模扩大到任何几何形状因数提供了机会。值得注意的是，微针贴片将允许在发展中世界无需医疗专业人员在场的情况下进行自我给药。Qβ技术具有高度适应性，可用于生产多种病毒株或病毒类型的候选疫苗及其递送装置。
