Background Older individuals and adults with certain chronic or immunocompromising health conditions are at increased risk of severe RSV disease. Methods In this phase 3 randomized trial of RSVpreF safety and immunogenicity in 18−59-year-olds at high-risk of severe RSV disease, participants were randomized 2:1 to 1 RSVpreF (120 µg) or placebo dose. Primary safety endpoints included reactogenicity events and adverse events (AEs) through 7 days and 1 month after vaccination, respectively, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) throughout the study. In primary analyses, immunogenicity elicited 1 month after RSVpreF was bridged to a randomly selected subset of ≥60-year-olds receiving RSVpreF from the immunogenicity subset in the pivotal phase 3 RENOIR trial, which demonstrated RSVpreF efficacy. Noninferiority was declared if 95% CI lower bounds were >0.667 (neutralizing titer adjusted geometric mean ratios) and >−10% (seroresponse rate differences) for RSV-A and RSV-B. Results Overall, 678 participants received RSVpreF (n=453) or placebo (n=225). Most reactogenicity events were mild/moderate; severe events occurred in ≤2.0% of participants overall. AE frequencies were similar in RSVpreF (7.1%) and placebo recipients (7.6%). No vaccine-related SAEs or NDCMCs were reported. One month after RSVpreF administration, noninferiority criteria were met in 18−59-year-olds versus ≥60-year-olds for RSV-A and RSV-B neutralizing titers and seroresponse rates. Conclusion RSVpreF was well tolerated with no safety concerns and demonstrated immunobridging to efficacy in 18−59-year-olds at high-risk of severe RSV disease versus ≥60-year-olds in whom efficacy was previously demonstrated, supporting use of RSVpreF to prevent RSV-associated disease in this population. NCT05842967.

中文翻译：

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18 至 <60 岁患有高危疾病的成人的二价 RSVpreF 疫苗


背景 患有某些慢性或免疫功能低下健康状况的老年人和成年人患严重 RSV 疾病的风险增加。方法 在这项针对 18-59 岁严重 RSV 疾病高危人群的 RSVpreF 安全性和免疫原性的 3 期随机试验中，参与者被随机分配 2：1 至 1 RSVpreF （120 μg） 或安慰剂剂量。主要安全终点分别包括接种疫苗后 7 天和 1 个月的反应原性事件和不良事件 （AE），以及整个研究过程中的严重 AE （SAE） 和新诊断的慢性疾病 （NDCMC）。在初步分析中，在关键 3 期 RENOIR 试验中，将 RSVpreF 桥接到随机选择的 ≥ 60 岁接受 RSVpreF 的人群子集后，免疫原性被桥接到接受 RSVpreF 的关键 3 期亚群中，这证明了 RSVpreF 的有效性。如果 RSV-A 和 RSV-B 的 95% CI 下限为 >0.667 （中和滴度调整的几何平均比值） 和 >-10% （血清反应率差异），则宣布非劣效性。结果 总体而言，678 名参与者接受了 RSVpreF （n=453） 或安慰剂 （n=225）。大多数反应原性事件为轻度/中度;总体上，严重事件发生在 ≤2.0% 的参与者中。RSVpreF （7.1%） 和安慰剂接受者 （7.6%） 的 AE 频率相似。未报告与疫苗相关的 SAE 或 NDCMC。RSVpreF 给药 1 个月后，18-59 岁与 ≥60 岁相比，RSV-A 和 RSV-B 中和滴度和血清反应率达到非劣效性标准。 结论 RSVpreF 耐受性良好，没有安全问题，并且在 18-59 岁严重 RSV 疾病高危人群中显示出免疫桥接疗效，而 ≥ 岁人群先前已证明疗效，支持使用 RSVpreF 预防该人群中的 RSV 相关疾病。NCT05842967。