Mazarakis Nadia, Toh Zheng Quan, Neal Eleanor, Bright Kathryn, Luu Skyy, Quah Leanne, Ng Yan Yung, Nguyen Cattram, Hart John, Do Lien Anh Ha, Rudel Anna, Dassanayake Shashini, Higgins Rachel A, Ong Darren Suryawijaya, Justice Fran, Moore Kerryn A, Watts Emma, Mahanty Siddhartha, Subbarao Kanta, Mulholland Kim, von Mollendorf Claire, Licciardi Paul V
Infection, Immunity, and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia.
Infection, Immunity, and Global Health, Murdoch Children's Research Institute, Melbourne, Australia.
J Infect. 2025 Mar;90(3):106447. doi: 10.1016/j.jinf.2025.106447. Epub 2025 Feb 18.
We conducted a randomised controlled trial (RCT) to compare immunogenicity, reactogenicity and safety one month after a fourth COVID-19 mRNA or protein vaccine dose.
This RCT recruited healthy adults in Melbourne, Australia, who had previously received three COVID-19 vaccine doses at least six months prior and had no SARS-CoV-2 infection in the last three months. The participants were randomised (1:1) to receive the bivalent mRNA vaccine (mRNA-1273.214/mRNA-1273.222, hereafter Moderna) or protein vaccine (NVX-CoV-2373, hereafter Novavax) as a fourth dose. A self-selected control group who elected not to receive an additional dose were also included. The co-primary endpoints compared immunogenicity at 28 days post-vaccination measured as binding antibodies (IgG against Ancestral and Omicron subvariants; BA.1, BA.4/5 and JN.1) between the two vaccine groups, and reactogenicity within one-week post-vaccination.
gov Identifier: NCT05543356.
Between Feb 28 and Oct 4, 2023, 496 participants were enrolled into the study. Participants were randomised into either the bivalent mRNA Moderna (n=177) or protein Novavax (n=176) vaccine groups, with n=143 allocated to the control group. The geometric mean ratio (GMR) of anti-Spike binding IgG antibody levels were higher for the Moderna vaccine compared to the Novavax vaccine at 28 days post-vaccination for all variants tested, including Ancestral (GMR: 2.11, 95% CI: 1.88 - 2.37), BA.1 (GMR: 2.32, 95% CI 2.04 - 2.63), BA.4/5 (GMR: 2.32, 95% CI: 2.04 - 2.65), and JN.1 (GMR: 2.40, 95% CI: 2.14 - 2.70). The frequency of any local and systemic reactions (grades 1-4) was higher for the Moderna vaccine (159/177; 89.8%) compared to the Novavax vaccine (130/176; 73.9%). Serious reactions (grade 3-4) between the groups were similar (11/177; 6.2%, versus 9/176; 5.1%, respectively).
At day 28 post-vaccination, higher immunogenicity was observed following Moderna vaccination compared to Novavax vaccination when given as a fourth dose in healthy adults for Ancestral and Omicron subvariants, including JN.1. However, local and systemic reactogenicity was higher in the Moderna vaccine group compared with the Novavax vaccine group. These results may have important implications for ongoing booster strategies.
我们进行了一项随机对照试验（RCT），以比较第四剂新冠病毒mRNA疫苗或蛋白疫苗接种一个月后的免疫原性、反应原性和安全性。
该RCT在澳大利亚墨尔本招募健康成年人，这些人此前至少在六个月前接种过三剂新冠病毒疫苗，且在过去三个月内没有感染过严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。参与者被随机（1:1）分配接受二价mRNA疫苗（mRNA-1273.214/mRNA-1273.222，以下简称Moderna）或蛋白疫苗（NVX-CoV-2373，以下简称Novavax）作为第四剂。还纳入了一个自行选择不接受额外一剂疫苗的对照组。共同主要终点比较了接种疫苗28天后两组疫苗之间作为结合抗体（针对原始毒株和奥密克戎亚变体的IgG；BA.1、BA.4/5和JN.1）测量的免疫原性，以及接种疫苗后一周内的反应原性。
美国国立医学图书馆临床试验注册库标识符：NCTU05543356。
在2023年2月28日至10月4日期间，496名参与者被纳入研究。参与者被随机分为二价mRNA的Moderna疫苗组（n = 177）或蛋白的Novavax疫苗组（n = 176），143人被分配到对照组。在接种疫苗28天后，对于所有测试变体，包括原始毒株（几何平均比[GMR]：2.11，95%置信区间[CI]：1.88 - 2.37）、BA.1（GMR：2.32，95% CI 2.04 - 2.63）、BA.4/5（GMR：2.32，95% CI：2.04 - 2.65）和JN.1（GMR：2.40，9% CI：2.14 - 2.70），Moderna疫苗的抗刺突结合IgG抗体水平的几何平均比高于Novavax疫苗。Moderna疫苗出现任何局部和全身反应（1 - 4级）的频率（159/177；89.8%）高于Novavax疫苗（130/176；73.9%）。两组之间的严重反应（3 - 4级）相似（分别为11/177；6.2%和9/176；5.1%）。
在接种疫苗第28天，在健康成年人中作为第四剂接种时，与Novavax疫苗相比，Moderna疫苗接种后对原始毒株和奥密克戎亚变体（包括JN.1）具有更高的免疫原性。然而，Moderna疫苗组的局部和全身反应原性高于Novavax疫苗组。这些结果可能对正在进行的加强免疫策略具有重要意义。
