A Scalable Manufacturing Approach to Single Dose Vaccination against HPV.
A Scalable Manufacturing Approach to Single Dose Vaccination against HPV.
复制标题
DOI：
10.3390/vaccines9010066
复制
发表时间：
2021-01-19
期刊：
影响因子：
7.8
通讯作者：
F Steinmetz N
中科院分区：
文献类型：
--
作者：
Shao S;A Ortega-Rivera O;Ray S;K Pokorski J;F Steinmetz N
人乳头瘤病毒（HPV）是一种全球流行的性传播病原体，导致大多数宫颈癌病例。HPV疫苗接种率仍然不理想，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，我们使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，用于单次给药和持续递送。将HPV 16衣壳蛋白L2的肽表位与噬菌体Qβ衍生的病毒样颗粒偶联，以增强其免疫原性。然后使用台式熔融加工系统将HPV-Qβ颗粒包封到聚（乳酸-共-乙醇酸）（PLGA）植入物中。在高温熔融加工期间，植入物促进HPV-Qβ颗粒的缓慢和持续释放，而不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剂相当，并在假病毒中和试验中获得保护。HPV-Qβ植入物提供了一个新的疫苗接种平台;由于熔融加工是如此通用，该技术提供了大规模升级到任何几何形状的机会。值得注意的是，在发展中国家，微针贴片将允许在没有医疗保健专业人员的情况下自我给药。Qβ技术具有高度适应性，允许生产候选疫苗及其用于多种病毒株或类型的递送装置。
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.
登录
查看更多内容
影响因子：
21.8
作者：
通讯作者：
--
DOI：
10.15585/mmwr.mm6429a3
发表时间：
2015-07-31
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Reagan-Steiner S;Yankey D;Jeyarajah J;Elam-Evans LD;Singleton JA;Curtis CR;MacNeil J;Markowitz LE;Stokley S
通讯作者：
Stokley S
影响因子：
7
作者：
Cirelli KM;Crotty S
通讯作者：
Crotty S
影响因子：
--
作者：
Day, Patricia M.;Pang, Yuk-Ying S.;Schiller, John T.
通讯作者：
Schiller, John T.
影响因子：
14
作者：
Shukla, Sourabh;Myers, Jay T.;Steinmetz, Nicole F.
通讯作者：
Steinmetz, Nicole F.