成人中BNT162b2疫苗与季节性灭活流感疫苗联合接种的安全性和免疫原性

Safety and Immunogenicity of the BNT162b2 Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Adults.

作者信息

Murdoch Louise, Quan Karen, Baber James A, Ho Agnes W Y, Zhang Ying, Xu Xia, Lu Claire, Cooper David, Koury Kenneth, Lockhart Stephen P, Anderson Annaliesa S, Türeci Özlem, Şahin Uğur, Swanson Kena A, Gruber William C, Kitchin Nicholas

机构信息

Emeritus Research, Camberwell, VIC, Australia.

Vaccine Clinical Research and Development, Pfizer Australia Pty Ltd, Sydney, NSW, Australia.

出版信息

Infect Dis Ther. 2023 Sep;12(9):2241-2258. doi: 10.1007/s40121-023-00863-5. Epub 2023 Sep 12.

INTRODUCTION

Vaccination is a critical tool for preventing coronavirus disease 2019 (COVID-19) and influenza illnesses. Coadministration of the COVID-19 vaccine, BNT162b2, with seasonal inactivated influenza vaccine (SIIV) can provide substantial benefits, including streamlining vaccine delivery.

METHODS

In this phase 3 study, healthy 18- to 64-year-olds who had received three previous doses of BNT162b2 were randomized (1:1) to the coadministration group (month 0, BNT162b2 + SIIV; month 1, placebo) or the separate-administration group (month 0, placebo + SIIV; month 1, BNT162b2). The primary immunogenicity objective was to demonstrate that the immune responses elicited by BNT162b2 and SIIV [measured by full-length S-binding immunoglobulin G (IgG) levels and strain-specific hemagglutination inhibition assay (HAI) titers against four influenza strains 1 month post-vaccination, respectively] when coadministered were noninferior to those elicited by either vaccine administered alone, based on a prespecified 1.5-fold noninferiority margin [lower bound 95% CI for geometric mean ratio (GMR) > 0.67]. Reactogenicity and adverse event (AE) rates were evaluated.

RESULTS

Randomized participants who received study vaccination (N = 1128; coadministration group, n = 564; separate-administration group, n = 564) had a median age of 39 years. Model-adjusted GMRs for coadministration to separate administration were 0.83 (95% CI 0.77, 0.89) for full-length S-binding IgG levels and 0.89-1.00 (lower bound of all 95% CIs > 0.67) for the four influenza strain-specific HAI titers, with all endpoints achieving the prespecified noninferiority criterion. Reactogenicity events were mostly mild or moderate when BNT162b2 was coadministered with SIIV. Serious AEs were reported in < 1% of participants within 1 month after any vaccination; none were considered vaccine-related.

CONCLUSIONS

BNT162b2 coadministered with SIIV elicited immune responses that were noninferior to those elicited by BNT162b2 alone and SIIV alone, and BNT162b2 had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of BNT162b2 and SIIV in adults.

TRIAL REGISTRATION

ClinicalTrials.gov registration: NCT05310084.

引言

接种疫苗是预防2019冠状病毒病（COVID-19）和流感疾病的关键手段。将COVID-19疫苗BNT162b2与季节性灭活流感疫苗（SIIV）同时接种可带来诸多益处，包括简化疫苗接种流程。

方法

在这项3期研究中，此前已接种过3剂BNT162b2的18至64岁健康受试者被随机（1:1）分为同时接种组（第0个月，BNT162b2 + SIIV；第1个月，安慰剂）或分开接种组（第0个月，安慰剂 + SIIV；第1个月，BNT162b2）。主要免疫原性目标是证明，基于预先设定的1.5倍非劣效性界值[几何平均比值（GMR）的95%置信区间下限>0.67]，同时接种BNT162b2和SIIV时所引发的免疫反应[分别通过接种疫苗1个月后全长S结合免疫球蛋白G（IgG）水平以及针对四种流感毒株的毒株特异性血凝抑制试验（HAI）效价来衡量]不劣于单独接种任何一种疫苗所引发的免疫反应。对接种反应和不良事件（AE）发生率进行了评估。

结果

接受研究疫苗接种的随机受试者（N = 1128；同时接种组，n = 564；分开接种组，n = 564）的中位年龄为39岁。同时接种与分开接种相比，全长S结合IgG水平的模型调整GMR为0.83（95%置信区间0.77，0.89），四种流感毒株特异性HAI效价的GMR为0.89至1.00（所有95%置信区间下限>0.67），所有终点均达到预先设定的非劣效性标准。当BNT162b2与SIIV同时接种时，接种反应事件大多为轻度或中度。在任何一次接种后1个月内，<1%的受试者报告了严重不良事件；无一例被认为与疫苗相关。