Recombinant herpes zoster (HZ) vaccines were reported as the most effective strategy to reduce the burden of herpes zoster and related complications. To ensure the quality, safety, and efficacy of recombinant HZ vaccines, comprehensive characterization of its antigen, recombinant glycoprotein E (RgE), is critical. However, due to the extreme complexity and heterogeneity of RgE, a single analytical platform is insufficient for comprehensive characterization. This study developed an innovative LC-MS-based workflow that combines multiple-parallel-protease digestion, various separation techniques (nano-flow LC, high-flow LC, and native separation), and high-resolution mass spectrometry (HR-MS) with multiple ion activation methods to achieve a comprehensive analysis of RgE. As a result, 21 and 21 O-glycosylation and phosphorylation sites were identified by EThcD-induced LC-MS/MS. Two N-glycosylation sites (N207 and N406) were identified with various N-glycans. The most abundant N-glycan for N207 was A2S2F. The top five N-glycans detected for N406 were also identified. Additionally, five disulfide linkages were detected for RgE. They were Cys 195-Cys 205, Cys 401-Cys 411, Cys 177-Cys 189, Cys 365-Cys 374, and Cys 356-Cys 382. For host cell protein (HCP) analysis, a high-sensitivity nano LC-MS/MS approach was applied, identifying 50 host cell proteins (HCPs), including two high-risk proteins, clusterin and peroxiredoxin-1. Additionally, molecular weight measurements obtained under both native and denatured conditions agreed well with the amino acid sequence acquired by peptide mapping. Following the optimization of the LC-MS workflow using RgE, the method was applied to evaluate recombinant zoster vaccines produced through different manufacturing processes. The results demonstrated that this workflow is highly effective for characterizing new recombinant zoster vaccines and may also serve as a valuable tool for the development of other complex recombinant vaccines.

2025-06-01·JOURNAL OF INFECTION AND CHEMOTHERAPY

Post-vaccinal seronegative autoimmune encephalitis following recombinant zoster vaccination in two immunocompetent patients

Article

作者: Abuzinadah, Ahmad R ; Madani, Salman T ; Alshehri, Ziad I ; Khoja, Abeer A ; Madani, Tariq A ; Alotaibi, Alaa A ; Abbas, Ghada M

BACKGROUND:

Varicella Zoster Virus (VZV) causes varicella as a primary infection and establishes latency in sensory ganglia. Reactivation in adults leads to herpes zoster (HZ). A highly effective recombinant zoster vaccine (Shingrix®) was recently developed to prevent HZ. While vaccine safety data is reassuring, we report two cases of post-vaccinal seronegative autoimmune encephalitis (AE) following the first dose of the Shingrix® vaccine. CASE 1: A 67-year-old male surgeon presented one week after receiving the vaccine with a one-day history of dizziness, fatigue, and insomnia, followed the next day by confusion, agitation, terrifying visual hallucinations, paraphasic errors, and echolalia. Brain imaging and cerebrospinal fluid (CSF) analysis were unremarkable. The CSF multiplex polymerase chain reaction (PCR) panel targeting 14 bacterial and viral pathogens associated with meningitis/encephalitis was negative. All known AE antibodies were also negative. The patient initially improved with empiric anti-meningitis/encephalitis therapy, including a two-day course of steroids but he relapsed shortly after stopping the steroids, necessitating re-admission. Pulse steroid therapy followed by plasmapheresis led to full recovery. CASE 2: A 50-year-old female pediatrician presented with acute confusion nine days after the Shingrix® vaccination. CSF analysis showed lymphocytic-predominant mild pleocytosis and elevated protein, but brain imaging was unremarkable. The CSF meningitis/encephalitis PCR panel and AE antibodies were negative. Pulse steroid therapy and plasmapheresis led to full recovery.

CONCLUSIONS:

These two cases highlight the potential for AE following the administration of the Shingrix® vaccine and underscore the importance of prompt recognition and aggressive immunotherapy to prevent morbidity and mortality.

2024-10-01·SEMINARS IN ARTHRITIS AND RHEUMATISM

Risk of incident gout following exposure to recombinant zoster vaccine in US adults aged ≥50 years

Article

作者: Platt, Richard ; Jamal-Allial, Aziza ; Messenger-Jones, Elizabeth ; Selvan, Mano ; Peters, Alexander ; Oraichi, Driss ; Alam, Sarah M ; Li, Dongdong ; Horgan, Casie ; Ziyadeh, Najat J ; Moyneur, Erick ; Spence, O'Mareen ; McMahill-Walraven, Cheryl N ; Pernar, Claire H ; Djibo, Djeneba Audrey ; Simon, Andrew L ; Ma, Qianli ; Daniels, Kimberly ; Franck, Valentine ; Yun, Huifeng ; Kluberg, Sheryl A ; Gamble, Susan ; Seifert, Harry

OBJECTIVE:

To assess whether recombinant zoster vaccine (RZV) is associated with an increased risk of new-onset gout among US adults aged ≥50 years.

METHODS:

We conducted a real-world, retrospective safety study with a self-controlled risk interval (SCRI) design using administrative claims data. We included health plan members aged ≥50 years with RZV exposure, followed by incident gout within 60 days. Days 1-30 following RZV exposure were considered the risk window (RW), and days 31-60 were considered the control window (CW). We estimated the risk ratio (RR) of gout in the RW versus CW, using a conditional Poisson model. The primary analysis estimated the risk of incident gout following any RZV dose. Sensitivity analyses evaluated dose 1- and dose 2-specific risks, risk among patients compliant with recommended dose spacing of 60-183 days, adjustment for seasonality, and restriction to the pre-COVID-19 era (before December 1, 2019).

RESULTS:

A total of 461,323 individuals received ≥1 RZV dose; we included 302 individuals (mean age 72.5 years; 66 % male) with evidence of new-onset gout within 60 days in SCRI analyses. A total of 153 (50.7 %) individuals had gout events in the RW and 149 (49.3 %) in the CW (RR 1.03; 95 % confidence interval 0.81, 1.29). All sensitivity analyses had consistent results, with no association of RZV with incident gout.

CONCLUSION:

In a population of US adults aged ≥50 years, there was no statistically significant increase in the risk of gout during the 30 days immediately after RZV exposure, compared with a subsequent 30-day CW.

项与重组带状疱疹疫苗 (康乐卫士) 相关的新闻（医药）

2023-09-26

·药创客

重磅！华诺泰重组带状疱疹疫苗（CHO细胞）获得临床试验批准

2023年9月25日，华诺泰的重组带状疱疹疫苗收到国家药品监督管理局核准签发的《药物临床试验批准通知书》，同意开展预防带状疱疹的Ⅰ、Ⅱ期临床试验。今年6月26日，该重组带状疱疹疫苗（HN101）临床试验申请获得国家药品监督管理局核准签发的受理通知书（受理号：CXSL2300431），历时刚好三个月。 HN101为华诺泰的产品管线中首个重磅级创新疫苗产品，自2020年初正式启动研发以来，仅仅用时3年就完成了临床前所有研究工作，获得了临床试验申请受理号，为国内同类产品研发速度之首。 HN101使用的佐剂为华诺泰自主研发的创新佐剂，具有完整的知识产权和广阔的延展性，为国内唯一一家实现符合GMP条件的中试生产、关键的核心原/辅材料储备充足、采购渠道稳定。目前华诺泰正在建设国内最大的新佐剂生产车间，预计2024年实现公斤级商业化规模生产，并实现全球销售。这不仅填补了国内空白、解决了我国佐剂领域“卡脖子”问题，也将引领中国制造转变为全球制造，确立中国在该领域内的重要地位。 HN101的临床前研究结果显示其细胞免疫和体液免疫在同等剂量下均优于现市售品，并表现出超强的免疫持久性；其安全性评价（GLP条件下）研究显示，单独的佐剂和整体疫苗安全性均优良。我们相信HN101是国内唯一可以媲美市售品的带疱疫苗，将会在下一步的临床试验中达到令人满意的临床终点。华诺泰针对HN101制定了系统的实施计划，并结合临床研究的推进速度，已启动了重组蛋白疫苗生产车间的建设，其中HN101生产车间的设计产能为2000万剂/年，同时布局了下一个超重量级产品RSV疫苗的生产车间。在当前疫苗行业强监管的政策环境下，华诺泰已自主拥有预防性生物制品的《药品生产许可证》，为HN101及后续产品的上市铺平了道路，将彻底解决人们相关疾病的困扰，造福国人。就在去年6月，华诺泰产业化基地正式签约落户成都温江（成都医学城cGMP标准厂房），总投资5亿元打造“华诺泰生产基地Ⅰ期”项目，规划建设面积3万余平方米，主要建设内容包括：3个疫苗原液生产车间，2个佐剂组分生产车间，2个制剂车间（冻干+预充）以及QC实验室、库房、办公室等。华诺泰落户成都医学城cGMP标准厂房华诺泰一直致力于新型疫苗佐剂的研发及产业化，经过不懈努力，继2021年9月QS-21佐剂组分完成中试生产后，华诺泰自主研发的3D-MLA佐剂组分也于2022年初完成了符合GMP条件下的200L发酵规模的中试生产，产品质量符合欧洲药典要求。在佐剂制剂开发方面，基于QS-21和3D-MLA的脂质体制剂HA201已顺利完成中试生产，批间稳定且质量符合药典要求，其他相关制剂将陆续完成中试生产，包括HA202、HA203等水包油制剂，以及多组分复合铝佐剂等。针对不同疫苗选择合适的佐剂制剂，通过小鼠免疫原性评价结表明，华诺泰的佐剂制剂在相应疫苗的抗体水平提升或免疫持久性等方面优势明显，相关结果显示如下：带状疱疹疫苗抗体水平在40周内仍维持较高水平流感疫苗佐剂组比无佐剂组二免后抗体水平可提高近万倍已完全解决两大难题新型佐剂的开发难度很大，特别是工艺放大的挑战，某些佐剂制剂配方中，通常具有难以表征和标准化的天然衍生成分，这导致了两个难题，一是工艺稳定放大较难，二是原材料来之不易。而华诺泰目前已完全解决了上述两个重大难点，并随着成都温江产业化基地落成后，将进入GMP级大规模生产阶段，相关产品一旦上市，将填补国内空白，解决“卡脖子”问题，同时将有助于更多、更好的新品种研制成功！内容来源于网络，如有侵权，请联系删除。

疫苗临床1期信使RNA临床2期

100 项与重组带状疱疹疫苗 (康乐卫士) 相关的药物交易

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