Background Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. The safety, tolerability, and immunogenicity of a 20-valent PCV (PCV20) were evaluated. Methods This pivotal phase 3, randomized, double-blind study enrolled adults into 3 age groups (≥60, 50–59, and 18–49 years) at US and Swedish sites. Participants were randomized to receive 1 PCV20 or 13-valent PCV (PCV13) dose. After 1 month, participants aged ≥60 years also received 1 dose of saline or 23-valent polysaccharide vaccine (PPSV23). Safety assessments included local reactions, systemic events, adverse events, serious adverse events, and newly diagnosed chronic medical conditions. Opsonophagocytic activity geometric mean titers 1 month after PCV20 were compared with 13 matched serotypes after PCV13 and 7 additional serotypes after PPSV23 in participants aged ≥60 years; noninferiority was declared if the lower bound of the 2-sided 95% confidence interval for the opsonophagocytic activity geometric mean titer ratio (ratio of PCV20/saline to PCV13/PPSV23 group) was >0.5. PCV20-elicited immune responses in younger participants were also bridged to those in 60–64-year-olds. Results The severity and frequency of prompted local reactions and systemic events were similar after PCV20 or PCV13; no safety concerns were identified. Primary immunogenicity objectives were met, with immune responses after PCV20 noninferior to 13 matched serotypes after PCV13 and to 6 additional PPSV23 serotypes in participants aged ≥60 years; serotype 8 missed the statistical noninferiority criterion. PCV20 induced robust responses to all 20 vaccine serotypes across age groups. Conclusions PCV20 was safe and well tolerated, with immunogenicity comparable to that of PCV13 or PPSV23. PCV20 is anticipated to expand protection against pneumococcal disease in adults. Clinical Trials Registration NCT03760146.

中文翻译：

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20 价肺炎球菌结合疫苗在 18 岁及以上成人中的安全性、耐受性和免疫原性的关键 3 期随机临床试验

背景 肺炎球菌结合疫苗 (PCV) 显着减少了肺炎球菌疾病，但非 PCV 血清型引起的疾病仍然存在。评估了 20 价 PCV (PCV20) 的安全性、耐受性和免疫原性。方法 这项关键的 3 期随机双盲研究在美国和瑞典将成年人分为 3 个年龄组（≥60、50–59 和 18–49 岁）。参与者被随机分配接受 1 剂 PCV20 或 13 价 PCV (PCV13)。1 个月后，≥60 岁的参与者还接受了 1 剂生理盐水或 23 价多糖疫苗 (PPSV23)。安全性评估包括局部反应、全身事件、不良事件、严重不良事件和新诊断的慢性疾病。在年龄≥60 岁的参与者中，将 PCV20 后 1 个月的调理吞噬活性几何平均滴度与 PCV13 后的 13 种匹配血清型和 PPSV23 后的 7 种额外血清型进行比较；如果调理吞噬活性几何平均滴度比（PCV20/生理盐水与 PCV13/PPSV23 组的比值）的 2 侧 95% 置信区间的下限＞0.5，则宣布非劣效性。PCV20 在年轻参与者中引发的免疫反应也与 60-64 岁人群中的免疫反应相联系。结果提示局部反应和全身事件的严重程度和频率在接种 PCV20 或 PCV13 后相似；没有发现安全问题。达到主要免疫原性目标，PCV20 后的免疫反应不劣于 PCV13 后的 13 种匹配血清型和 60 岁以上参与者的 6 种额外 PPSV23 血清型；血清型 8 未达到统计非劣效性标准。PCV20 在不同年龄组对所有 20 种疫苗血清型产生强烈反应。结论 PCV20 安全且耐受性良好，其免疫原性与 PCV13 或 PPSV23 相当。预计 PCV20 将扩大对成人肺炎球菌疾病的保护。临床试验注册 NCT03760146。