在≥12 岁人群中使用二价奥密克戎 BA.4/BA.5 适应型 BNT162b2 加强针。

A Bivalent Omicron-BA.4/BA.5-Adapted BNT162b2 Booster in ≥12-Year-Olds.

机构信息

CNS Healthcare, Memphis, Tennessee, USA.

Vaccine Research and Development, Pfizer, Hurley, United Kingdom.

出版信息

Clin Infect Dis. 2024 May 15;78(5):1194-1203. doi: 10.1093/cid/ciad718.

DOI:10.1093/cid/ciad718

PMID:38016021

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11093671/

Abstract

BACKGROUND

Protection against contemporary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants requires sequence-adapted vaccines.

METHODS

In this ongoing phase 2/3 trial, 12-17-year-olds (n = 108), 18-55-year-olds (n = 313), and >55-year-olds (n = 306) who previously received 3 original BNT162b2 30-µg doses, received a fourth dose (second booster) of 30-µg bivalent original/Omicron-BA.4/BA.5-adapted BNT162b2 (BNT162b2-Omi.BA.4/BA.5). For comparisons with original BNT162b2, participants were selected from another phase 3 trial. Immunologic superiority 1 month after vaccination, with respect to 50% neutralizing titers (lower bound [LB] of 2-sided 95% confidence interval [CI] for geometric mean ratio [GMR], >1), and noninferiority with respect to seroresponse rates (LB of 2-sided 95% CI for rate difference, greater than -5%), for Omicron BA.4/BA.5 were assessed in >55-year-olds versus original BNT162b2 as a second booster. Noninferiority with respect to neutralizing titer level (LB of 2-sided 95% CI for GMR, > 0.67) and seroresponse rate (LB of 2-sided 95% CI for rate difference, greater than -10%) of Omicron BA.4/BA.5 immune response for BNT162b2-Omi.BA.4/BA.5 in 18-55 versus >55-year-olds was assessed.

RESULTS

One month after vaccination in >55-year-olds, the model-adjusted GMR of Omicron BA.4/BA.5 neutralizing titers for the BNT162b2-Omi.BA.4/BA.5 versus BNT162b2 groups (2.91 [95% CI, 2.45-3.44]) demonstrated the superiority of BNT162b2-Omi.BA.4/BA.5. Adjusted difference in the percentages of >55-year-olds with seroresponse (26.77% [95% CI, 19.59-33.95]) showed noninferiority of BNT162b2-Omi.BA.4/BA.5 to BNT162b2. Noninferiority of BNT162b2-Omi.BA.4/BA.5 in 18-55-year-olds compared with >55-year-olds was met for model-adjusted GMR and seroresponse. Geometric mean titers in 12-17-year-olds increased from baseline to 1 month after vaccination. The BNT162b2-Omi.BA.4/BA.5 safety profile was similar to the profiles for booster doses of bivalent Omicron BA.1-modified BNT162b2 and original BNT162b2 reported in previous studies.

CONCLUSIONS

Based on immunogenicity and safety data up to 1 month after vaccination in participants who previously received 3 original BNT162b2 doses, a BNT162b2-Omi.BA.4/BA.5 30-µg booster has a favorable benefit-risk profile.

CLINICAL TRIALS REGISTRATION

NCT05472038.

摘要

背景

预防当代严重急性呼吸系统综合征冠状病毒 2 （SARS-CoV-2）变体需要进行序列适配的疫苗。

方法

在这项正在进行的 2/3 期试验中，12-17 岁（n=108）、18-55 岁（n=313）和>55 岁（n=306）的个体先前接受了 3 剂原始 BNT162b2 30μg 剂量，接种了第四剂（第二剂加强针）30μg 双价原始/Omicron-BA.4/BA.5 适应型 BNT162b2（BNT162b2-Omi.BA.4/BA.5）。为了与原始 BNT162b2 进行比较，参与者从另一项 3 期试验中选择。接种后 1 个月，评估了对 50%中和滴度（几何均数比[GMR]双侧 95%置信区间[CI]下限大于 1）的免疫优势，以及对血清反应率（双侧 95%CI 下限为率差大于-5%）的非劣效性，在>55 岁的个体中，Omicron BA.4/BA.5 对原始 BNT162b2 作为第二剂加强针。在 18-55 岁的个体中，评估了对 Omicron BA.4/BA.5 免疫应答的中和滴度水平（双侧 95%CI 的 GMR 下限大于 0.67）和血清反应率（双侧 95%CI 的率差下限大于-10%）的非劣效性，BNT162b2-Omi.BA.4/BA.5 在 18-55 岁与>55 岁的个体中。

结果

在>55 岁的个体中，接种后 1 个月，BNT162b2-Omi.BA.4/BA.5 组与 BNT162b2 组的 Omicron BA.4/BA.5 中和滴度的模型调整 GMR（2.91[95%CI，2.45-3.44]）显示 BNT162b2-Omi.BA.4/BA.5 的优越性。>55 岁个体中血清反应率（26.77%[95%CI，19.59-33.95]）的调整差异表明 BNT162b2-Omi.BA.4/BA.5 与 BNT162b2 相似。在 18-55 岁的个体中，与>55 岁的个体相比，BNT162b2-Omi.BA.4/BA.5 达到了模型调整 GMR 和血清反应的非劣效性。12-17 岁个体的几何平均滴度从基线增加到接种后 1 个月。BNT162b2-Omi.BA.4/BA.5 的安全性特征与先前研究中报告的双价 Omicron BA.1 修饰型 BNT162b2 和原始 BNT162b2 加强针的安全性特征相似。