MF59 佐剂的 SARS-CoV-2 刺突糖蛋白夹心法疫苗在 18-55 岁或≥56 岁成年人中的长期安全性和免疫原性：一项随机、双盲、安慰剂对照、1 期临床试验的 12 个月结果。
Long-term safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2 in adults aged 18-55 years or ≥56 years: 12-month results from a randomised, double-blind, placebo-controlled, phase 1 trial.
机构信息
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia; The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
出版信息
EBioMedicine. 2023 Nov;97:104842. doi: 10.1016/j.ebiom.2023.104842. Epub 2023 Oct 20.
BACKGROUND
We previously demonstrated the safety and immunogenicity of an MF59-adjuvanted COVID-19 vaccine based on the SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a molecular clamp using HIV-1 glycoprotein 41 sequences. Here, we describe 12-month results in adults aged 18-55 years and ≥56 years.
METHODS
Phase 1, double-blind, placebo-controlled trial conducted in Australia (July 2020-December 2021; ClinicalTrials.govNCT04495933; active, not recruiting). Healthy adults (Part 1: 18-55 years; Part 2: ≥56 years) received two doses of placebo, 5 μg, 15 μg, or 45 μg vaccine, or one 45 μg dose of vaccine followed by placebo (Part 1 only), 28 days apart (n = 216; 24 per group). Safety, humoral immunogenicity (including against virus variants), and cellular immunogenicity were assessed to day 394 (12 months after second dose). Effects of subsequent COVID-19 vaccination on humoral responses were examined.
FINDINGS
All two-dose vaccine regimens were well tolerated and elicited strong antigen-specific and neutralising humoral responses, and CD4 T-cell responses, by day 43 in younger and older adults, although cellular responses were lower in older adults. Humoral responses waned by day 209 but were boosted in those receiving authorised vaccines. Neutralising activity against Delta and Omicron variants was present but lower than against the Wuhan strain. Cross-reactivity in HIV diagnostic tests declined over time but remained detectable in most participants.
INTERPRETATION
The SARS-CoV-2 molecular clamp vaccine is well tolerated and evokes robust immune responses in adults of all ages. Although the HIV glycoprotein 41-based molecular clamp is not being progressed, the clamp concept represents a viable platform for vaccine development.
FUNDING
This study was funded by the Coalition for Epidemic Preparedness Innovations, the National Health and Medical Research Council of Australia, and the Queensland Government.
背景
我们之前展示了一种基于 SARS-CoV-2 刺突糖蛋白的 MF59 佐剂 COVID-19 疫苗的安全性和免疫原性，该疫苗通过分子夹稳定在融合前构象中，分子夹使用 HIV-1 糖蛋白 41 序列。在此，我们描述了 18-55 岁和≥56 岁成年人的 12 个月结果。
方法
这是一项在澳大利亚进行的 1 期、双盲、安慰剂对照试验（2020 年 7 月至 2021 年 12 月；ClinicalTrials.govNCT04495933；活跃，不招募）。健康成年人（第 1 部分：18-55 岁；第 2 部分：≥56 岁）接受了安慰剂、5μg、15μg 或 45μg 疫苗的两剂，或仅第 1 部分的一剂 45μg 疫苗和随后的安慰剂（第 1 部分），间隔 28 天（n=216；每组 24 人）。在第 394 天（第二次给药后 12 个月）评估安全性、体液免疫原性（包括针对病毒变体）和细胞免疫原性。检查随后 COVID-19 疫苗接种对体液反应的影响。
结果
在年轻和老年成年人中，所有两剂疫苗方案均耐受良好，并且在第 43 天产生了强烈的抗原特异性和中和性体液反应以及 CD4 T 细胞反应，尽管老年成年人的细胞反应较低。体液反应在第 209 天减弱，但在接受授权疫苗的人群中得到了增强。对 Delta 和 Omicron 变体的中和活性存在，但低于对武汉株的中和活性。在 HIV 诊断测试中的交叉反应随时间而下降，但在大多数参与者中仍可检测到。
结论
SARS-CoV-2 分子夹疫苗在所有年龄段的成年人中均耐受良好，并引起强烈的免疫反应。尽管基于 HIV 糖蛋白 41 的分子夹未得到进一步发展，但夹概念代表了疫苗开发的可行平台。
资金
这项研究由传染病防范创新联盟、澳大利亚国家卫生和医学研究委员会以及昆士兰州政府资助。
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