55岁以上成人的二价Omicron BA.1-适应性BNT162b2助推剂

SCI 10 February 2023

Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years 

(N Engl J Med I F: 91.25)

P. Winokur, J. Gayed, D. Fitz‐Patrick, S.J. Thomas, O. Diya, S. Lockhart, X. Xu, Y. Zhang, V. Bangad, H.I. Schwartz, D. Denham, J.F. Cardona, L. Usdan, J. Ginis, F.J. Mensa, J. Zou, X. Xie, P.‐Y. Shi, C. Lu, S. Buitrago, I.L. Scully, D. Cooper, K. Koury, K.U. Jansen, Ö. Türeci, U. Şahin, K.A. Swanson, W.C. Gruber, and N. Kitchin, for the C4591031 Clinical Trial Group 

N Engl J Med 2023;388:214-27.DOI: 10.1056/NEJMoa2213082

BACKGROUND 背景   

The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. 

严重急性呼吸道综合征冠状病毒2的免疫逃逸变种的出现，使得我们有必要使用序列适应性疫苗来提供对2019年冠状病毒疾病的保护。

METHODS 方法   

In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1– adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2+15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2+30 μg of monovalent BA.1) of BA.1–adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and non- inferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. 

在一项正在进行的3期试验中，55岁以上、曾接受过三次30微克BNT162b2疫苗的成人被随机分配接受30微克或60微克BNT162b2、30微克或60微克单价B.1 .1.529（微克）BA.1适应的BNT162b2（单价BA.1），或30微克（15微克BNT162b2+15微克单价BA.1）或60微克（30微克BNT162b2+30微克单价BA.1）的BA.1适应的BNT162b2（二价BA.1）。主要目标是确定BA.1适应性疫苗对BNT162b2（30μg）的优越性（关于对BA.1的50%中和滴度[NT50]）和非劣质性（关于血清反应）。次要目标是确定二价BA.1对BNT162b2（30μg）在中和祖先菌株方面的非劣势。探索性分析评估了对Omicron BA.4、BA.5和BA.2.75亚变种的免疫反应。

RESULTS 结果 

A total of 1846 participants underwent randomization. At 1 month after vaccina- tion, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutral- izing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT50 geo- metric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was non- inferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4–BA.5 and BA.2.75 neutralizing titers were numeri- cally higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). 

共有1846名参与者接受了随机分组。疫苗接种后1个月，二价BA.1（30微克和60微克）和单价BA.1（60微克）对BA.1显示出中和活性。的中和活性优于BNT162b2（30μg），其NT50地理计量平均比（GMRs）分别为1.56（95%置信区间[CI]，1.17至2.08）、1.97（95%CI，1.45至2.68）和3.15（95%CI，2.38至4.16）。在对BA.1的血清反应方面，二价BA.1（两种剂量）和单价BA.1（60微克）也不劣于BNT162b2（30微克）；组间差异在10.9至29.1个百分点之间。二价BA.1（任一剂量）对祖传菌株的中和活性不逊于BNT162b2（30μg），NT50 GMRs分别为0.99（95%CI，0.82至1.20）和1.30（95%CI，1.07至1.58）。30μg二价BA.1的BA.4-BA.5和BA.2.75的中和滴度比30μg BNT162b2的要高。单价或二价BA.1的安全状况与BNT162b2（30μg）相似。不良事件在30μg单价BA.1（8.5%）和60μg二价BA.1（10.4%）组中比其他组（3.6至6.6%）更常见。

CONCLUSIONS 结论   

The candidate monovalent or bivalent omicron BA.1–adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing re- sponses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutral- ized BA.4, BA.5, and BA.2.75 strains.

候选的单价或二价Omicron BA.1适应性疫苗具有与BNT162b2（30μg）相似的安全性，对祖先和Omicron BA.1菌株诱发了大量的中和反应，并在较小程度上中和了BA.4、BA.5和BA.2.75菌株。

打赏