成人中自扩增mRNA新冠疫苗（ARCT-2303）单独或与季节性灭活流感疫苗联合接种的免疫原性和安全性：一项3期随机对照、观察者盲法、多中心研究。
Immunogenicity and safety of self-amplifying mRNA COVID-19 vaccine (ARCT-2303), with or without co-administration of seasonal inactivated influenza vaccine in adults: a phase 3, randomised, controlled, observer-blind, multicentre study.
作者信息
Giles Michelle L, Tabora Charissa, Baccarini Carmen, Barrientos Leonela, Vargas Javier Cespedes, Montellano May Emmeline, Nguyen Paul, Deshmukh Sachin, Neville Munro, Hohenboken Matthew, van Boxmeer Josephine, Jin Hongfan, Bugarini Roberto, Liu Xuexuan, Walson Judd L, Verhoeven Carole, Smolenov Igor
机构信息
Peter Doherty Institute for Immunity and Infection, The University of Melbourne, Australia.
Tropical Disease Foundation Inc., Makati, Metro Manila, Philippines.
出版信息
EClinicalMedicine. 2025 Aug 20;87:103428. doi: 10.1016/j.eclinm.2025.103428. eCollection 2025 Sep.
BACKGROUND
A recently licenced self-amplifying mRNA (sa-mRNA) COVID-19 vaccine induces a robust, broad, and long-lasting immune response, extending the arsenal of efficacious COVID-19 countermeasures. We ran a clinical study to assess the benefits of vaccine strain update and the feasibility of co-administration with influenza vaccines.
METHODS
Between March 27, 2024 and April 10, 2025, we performed a randomised, observer-blind, placebo-controlled, phase 3 study with 1499 adult participants to compare immune responses of sa-mRNA vaccine, encoding spike glycoprotein of the XBB.1.5 subvariant (ARCT-2303), with vaccine encoding the ancestral strain (ARCT-154), as measured by geometric mean titres of neutralising antibodies and SARS-CoV-2 neutralising antibody seroconversion rates against the Omicron XBB.1.5, and to assess the immunological non-inferiority of co-administered ARCT-2303 and influenza vaccines compared with separately administered vaccines, as measured by neutralising antibodies against Omicron XBB.1.5.6 and haemagglutinin inhibition against influenza vaccine strains. Reactogenicity (adverse events on Days 1-7) and safety (adverse events on Days 1-181) were also assessed. The trial was registered on ClinicalTrials.gov (identifier NCT06279871).
FINDINGS
The geometric mean ratio (ARCT-2303/ARCT-154) of neutralising antibodies against Omicron XBB.1.5.6 on Day 29 was 2.7 (95% confidence interval (CI): 2.3-3.2), and the seroconversion rate difference was 28.4% (21.8-34.9); both met the prespecified superiority criteria. Concomitant administration of ARCT-2303 had no impact on the immune response to the quadrivalent influenza vaccine antigens, whether the non-adjuvanted vaccine given to 18‒64 year-old adults or the adjuvanted vaccine given to adults 65 years and older. The non-inferiority of the immune response against Omicron XBB.1.5.6 was also demonstrated when ARCT-2303 was co-administered or administered separately.
INTERPRETATION
We conclude that ARCT-2303 induces a robust immune response against the vaccine variant of SARS-CoV-2 and can be co-administered with licenced influenza vaccines in adults with no impact on the safety or immunogenicity of either vaccine.
FUNDING
The study is funded by CSL under a collaboration agreement with Arcturus Therapeutics.
背景
一种最近获批的自我扩增信使核糖核酸（sa-mRNA）新冠疫苗可诱导强烈、广泛且持久的免疫反应，扩充了有效的新冠应对措施。我们开展了一项临床研究，以评估疫苗毒株更新的益处以及与流感疫苗联合接种的可行性。
方法
在2024年3月27日至2025年4月10日期间，我们进行了一项随机、观察者盲法、安慰剂对照的3期研究，纳入1499名成年参与者，比较编码XBB.1.5亚变体刺突糖蛋白的sa-mRNA疫苗（ARCT-2303）与编码原始毒株的疫苗（ARCT-154）的免疫反应，通过针对奥密克戎XBB.1.5的中和抗体几何平均滴度和SARS-CoV-2中和抗体血清转化率来衡量，并评估联合接种ARCT-2303和流感疫苗与分别接种疫苗相比的免疫非劣效性，通过针对奥密克戎XBB.1.5.6的中和抗体和针对流感疫苗毒株的血凝抑制来衡量。还评估了反应原性（第1 - 7天的不良事件）和安全性（第1 - 181天的不良事件）。该试验已在ClinicalTrials.gov上注册（标识符NCT06279871）。
结果
第29天时，针对奥密克戎XBB.1.5.6的中和抗体几何平均比值（ARCT-2303/ARCT-154）为2.7（95%置信区间（CI）：2.3 - 3.2），血清转化率差异为28.4%（21.8 - 34.9）；两者均符合预先设定的优效性标准。无论给18至64岁成年人接种的无佐剂疫苗还是给65岁及以上成年人接种的佐剂疫苗，联合接种ARCT-2303对四价流感疫苗抗原的免疫反应均无影响。当ARCT-2303联合接种或单独接种时，针对奥密克戎XBB.1.5.6的免疫反应非劣效性也得到了证实。
解读
我们得出结论，ARCT-2303可诱导针对SARS-CoV-2疫苗变体强大的免疫反应，并且可以与获批的流感疫苗在成年人中联合接种，对两种疫苗的安全性或免疫原性均无影响。
资金来源
该研究由赛诺菲（CSL）根据与Arcturus Therapeutics的合作协议资助。
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