{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:43:04Z","timestamp":1785307384734,"version":"3.55.0"},"reference-count":41,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"unspecified","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canada Institutes of Health Research","doi-asserted-by":"crossref","award":["EG9-179473"],"award-info":[{"award-number":["EG9-179473"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,2,27]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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\u20135 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      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\u201389 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\n                      <jats:italic>Lacticaseibacillus rhamnosus<\/jats:italic>\n                      and\n                      <jats:italic>Lacticaseibacillus casei<\/jats:italic>\n                      6\u00d710\n                      <jats:sup>9<\/jats:sup>\n                      \u2009CFU\/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\u2009months 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>\n                      The study was approved by Research Ethics Board of the\n                      <jats:italic>Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et des Services Sociaux de l\u2019Estrie- Centre Hospitalier Universitaire de Sherbrooke<\/jats:italic>\n                      (\n                      <jats:italic>CIUSSS de l\u2019Estrie-CHUS<\/jats:italic>\n                      ) and the\n                      <jats:italic>CHU de Qu\u00e9bec-Universit\u00e9 Laval # MP-31-2022-<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05195151\">NCT05195151<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-088231","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T04:32:00Z","timestamp":1742531520000},"page":"e088231","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["<b>P<\/b>\n                    robiotics\n                    <b>i<\/b>\n                    nfluencing\n                    <b>r<\/b>\n                    esponse of\n                    <b>a<\/b>\n                    ntibodies over\n                    <b>t<\/b>\n                    ime in\n                    <b>s<\/b>\n                    eniors after\n                    <b>CO<\/b>\n                    VID-19\n                    <b>v<\/b>\n                    accine (PIRATES-COV): a randomised controlled trial protocol"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct05195151","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jean-Charles","family":"Pasquier","sequence":"first","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Universit\u00e9 de Montr\u00e9al, Montreal, Qu\u00e9bec, Canada"},{"name":"CHUM, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Plourde","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, 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