Pasquier Jean-Charles, Plourde Mélanie, Ramanathan Sheela, Chaillet N, Boivin Guy, Laforest-Lapointe Isabelle, Allard-Chamard Hugues, Baron Geneviève, Beaulieu Jean-François, Fülöp Tamas, Généreux Mélissa, Mâsse Benoît, Robitaille Julie, Valiquette Louis, Bilodeau Sarah, H Buch Danielle, Piche Alain
Department of Obstetrics & Gynaecology, Université de Montréal, Montreal, Québec, Canada
CHUM, Montreal, Québec, Canada.
BMJ Open. 2025 Mar 18;15(3):e088231. doi: 10.1136/bmjopen-2024-088231.
The elderly are particularly vulnerable to morbidity and mortality from COVID-19, the disease caused by the SARS-CoV-2. Approximately 20% of the elderly showed no antibodies 3-5 months post-second dose of the COVID-19 vaccine. As probiotics have been shown to increase influenza-specific antibody levels post-influenza vaccination, we aim to reduce the percentage of participants without antibodies against the SARS-CoV-2 spike protein receptor-binding domain (anti-S1-RBD) at 6 months post-vaccination.
Our study design is a double-blind randomised controlled trial, using intention-to-treat analysis. Eligible participants are a purposive sample of 688 adults aged 65-89 years, in Quebec, Canada, not diagnosed with COVID-19 in the 3 months prior to recruitment and who wish to receive a government-recommended mRNA booster (Pfizer-BioNTech, Moderna) vaccine. The intervention consists of one capsule/day of a probiotic dietary supplement of and 6×10 CFU/capsule or a placebo, for 15 days pre-booster and post-booster vaccine. All participants provide dried blood spot samples at three timepoints (inclusion, 3 and 6 months post-vaccination) and a stool sample for microbiome analysis. A subgroup of 100 participants living near Sherbrooke, Quebec, is expected to volunteer for two onsite blood-test visits (at inclusion and 6 months post-vaccination). The primary outcome is the percentage of participants without anti-S1-RBD antibodies at 6 months post-vaccination. Secondary outcomes include longitudinal analysis of anti-S1-RBD and anti-N antibodies at three timepoints. In the subgroup, serum levels of neutralising antibodies will be determined at inclusion and 6 months post-vaccination. Probiotic and vaccine side effects are monitored. At the end of the study, we expect to identify the adjuvant effect of probiotic on vaccine-induced immune response.
The study was approved by Research Ethics Board of the () and the 4598 as well as Health Canada. All participants will provide informed consent. Results will be disseminated to the scientific community and to all networks related in this research.
NCT05195151.
老年人尤其容易因感染由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）而发病和死亡。约20%的老年人在接种第二剂COVID-19疫苗后3至5个月未产生抗体。由于益生菌已被证明可提高流感疫苗接种后流感特异性抗体水平，我们旨在降低接种疫苗6个月后未产生针对SARS-CoV-2刺突蛋白受体结合域（抗S1-RBD）抗体的参与者比例。
我们的研究设计为双盲随机对照试验，采用意向性分析。符合条件的参与者是从加拿大魁北克省688名65至89岁成年人中选取的有目的样本，在招募前3个月未被诊断为COVID-19，且希望接种政府推荐的mRNA加强针（辉瑞-生物科技、莫德纳）疫苗。干预措施包括在加强针疫苗接种前和接种后15天，每天服用一粒含有 和6×10 CFU/胶囊的益生菌膳食补充剂胶囊或安慰剂。所有参与者在三个时间点（纳入时、接种疫苗后3个月和6个月）提供干血斑样本，并提供一份粪便样本用于微生物组分析。预计居住在魁北克省舍布鲁克附近的100名参与者将自愿参加两次现场血液检测（纳入时和接种疫苗后6个月）。主要结局是接种疫苗6个月后未产生抗S1-RBD抗体的参与者比例。次要结局包括在三个时间点对抗S1-RBD和抗N抗体的纵向分析。在该亚组中，将在纳入时和接种疫苗后6个月测定中和抗体的血清水平。监测益生菌和疫苗的副作用。在研究结束时，我们期望确定益生菌对疫苗诱导免疫反应的佐剂作用。
该研究已获得（）研究伦理委员会以及4598和加拿大卫生部的批准。所有参与者将提供知情同意书。研究结果将传播给科学界以及本研究相关的所有网络。
NCT05195151。
