Peninsula Research Associates, Rolling Hills Estates, California, USA.
Vaccine Research and Development, Pfizer Ltd, Hurley, UK.
J Pediatric Infect Dis Soc. 2024 Aug 24;13(8):421-429. doi: 10.1093/jpids/piae062.
With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important.
We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated.
In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation.
These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.
由于严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的未来流行病学和演变尚不确定，在儿科人群中使用安全有效的 2019 冠状病毒病 (COVID-19) 疫苗仍然很重要。
我们报告了一项正在进行的 1/2/3 期主研究（NCT05543616）的两个开放标签子研究的数据，该研究调查了一种变异适应的二价 COVID-19 疫苗的安全性和免疫原性，该疫苗编码了原始和奥密克戎 BA.4/BA.5 刺突蛋白（二价 BNT162b2）。这里介绍的开放标签组评估了在先前接受过三剂原始（单价）BNT162b2 的 6 个月至<12 岁儿童中，第 4 剂二价 BNT162b2 的安全性和免疫原性。在 6 个月至<5 岁的儿童中，主要免疫原性目标是证明与奥密克戎 BA.4/BA.5 相比具有优越性（中和滴度）和非劣效性（血清反应率），与 SARS-CoV-2 原始株相比具有非劣效性（中和滴度和血清反应率），与在关键儿科研究（NCT04816643）中接受三剂原始 BNT162b2 的匹配组相比，接受二价 BNT162b2 第 4 剂的参与者。在 5-<12 岁的儿童中，主要免疫原性比较是描述性的。接种后的不良反应和安全性进行了评估。
在 6 个月至<5 岁的儿童中，与原始 BNT162b2 第 3 剂相比，二价 BNT162b2 第 4 剂在针对奥密克戎 BA.4/BA.5 和原始株方面达到了预先设定的免疫原性优越性和非劣效性标准。在 5-<12 岁的儿童中，二价 BNT162b2 诱导的奥密克戎 BA.4/BA.5 和原始株中和滴度与原始 BNT162b2 第 3 剂相当。6 个月至<12 岁儿童中，二价 BNT162b2 第 4 剂的安全性与原始 BNT162b2 第 4 剂一致。一般来说，不良反应为轻度至中度。没有不良事件导致停药。
这些安全性和免疫原性数据支持在<12 岁儿童中使用变异适应的 BNT162b2 具有良好的获益风险比。
