Abstract：
Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.
摘要：
尽管目前使用多糖和结合疫苗，肺炎球菌疾病在老年人中仍然很普遍.VAX-24是一种含有eCRM的24价肺炎球菌结合疫苗（PCV），一种具有非天然氨基酸（对叠氮基甲基-L-苯丙氨酸）的专有载体蛋白，可与已被小分子接头（二苯并环辛炔）激活的肺炎球菌多糖进行位点特异性缀合。利用点击化学的位点特异性缀合能够实现T细胞表位的一致暴露，载体蛋白与肺炎球菌多糖比率降低，并增强制造工艺的一致性，通过增加血清型覆盖率同时最小化载体抑制来改善PCV。65岁或以上的健康成年人以1：1：1：1的比例随机分配，以3种剂量水平（1.1、2.2或2.2或4.4mcg的混合剂量）或Prevnar20®（PCV20）中的1种单次注射VAX-24。主要结局指标为疫苗接种后7天内的局部和全身事件，1个月内未经请求的不良事件（AE），和严重的AE，医疗护理AE，或在接种疫苗后6个月内新发的慢性病。在疫苗接种前和疫苗接种后1个月测量血清型特异性调理吞噬活性(OPA)和免疫球蛋白G(IgG)。在207名参与者中，200人完成了审判。三种VAX-24剂量和PCV20的安全性比较。所有24种血清型均观察到稳健的OPA和IgG免疫应答。平均而言,与PCV20相比,对VAX-242.2mcg剂量的免疫反应相似或更高.在≥65岁的成年人中，VAX-24在疫苗接种后6个月内具有与PCV20相似的安全性，并对所有24种血清型诱导了强烈的OPA和IgG反应。支持先前的数据显示位点特异性缀合允许增加的血清型覆盖率,与其他PCV相比具有相似或更高的免疫应答。这项2期研究的结果进一步支持在3期试验中使用VAX-242.2mcg剂量。Clinicaltrials.gov:NCT05297578.
