{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:14:38Z","timestamp":1792005278996,"version":"4.4.0"},"reference-count":69,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"unspecified","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Vaccine-specific immune responses vary between populations and are\n                            often impaired in low income, rural settings. Drivers of these\n                            differences are not fully elucidated, hampering identification of\n                            strategies for optimising vaccine effectiveness. We hypothesise that\n                            urban\u2013rural (and regional and international) differences in vaccine\n                            responses are mediated to an important extent by differential exposure\n                            to chronic infections, particularly parasitic infections.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                        <jats:title>Methods and analysis<\/jats:title>\n                        <jats:p>Three related trials sharing core elements of study design and\n                            procedures (allowing comparison of outcomes across the trials) will test\n                            the effects of (1) individually randomised intervention against\n                            schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus\n                            Calmette-Gu\u00e9rin (BCG) revaccination (trial C), on a common set of\n                            vaccine responses. We will enrol adolescents from Ugandan schools in\n                            rural high-schistosomiasis (trial A) and rural high-malaria (trial B)\n                            settings and from an established urban birth cohort (trial C). All\n                            participants will receive BCG on day \u20180\u2019; yellow fever, oral typhoid and\n                            human papilloma virus (HPV) vaccines at week 4; and HPV and\n                            tetanus\/diphtheria booster vaccine at week 28. Primary outcomes are\n                            BCG-specific IFN-\u03b3 responses (8\u2009weeks after BCG) and for other vaccines,\n                            antibody responses to key vaccine antigens at 4\u2009weeks after\n                            immunisation. Secondary analyses will determine effects of interventions\n                            on correlates of protective immunity, vaccine response waning, priming\n                            versus boosting immunisations, and parasite infection status and\n                            intensity. Overarching analyses will compare outcomes between the three\n                            trial settings. Sample archives will offer opportunities for exploratory\n                            evaluation of the role of immunological and \u2018trans-kingdom\u2019 mediators in\n                            parasite modulation of vaccine-specific responses.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                        <jats:title>Ethics and dissemination<\/jats:title>\n                        <jats:p>Ethics approval has been obtained from relevant Ugandan and UK\n                            ethics committees. Results will be shared with Uganda Ministry of\n                            Health, relevant district councils, community leaders and study\n                            participants. Further dissemination will be done through conference\n                            proceedings and publications.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                        <jats:title>Trial registration numbers<\/jats:title>\n                        <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT60517191\">NCT60517191<\/jats:ext-link>,<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT62041885\">NCT62041885<\/jats:ext-link>,<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT10482904\">NCT10482904<\/jats:ext-link>.<\/jats:p>\n                    <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-040425","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T14:37:09Z","timestamp":1667572629000},"page":"e040425","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Population differences in vaccine responses (POPVAC): scientific\n                        rationale and cross-cutting analyses for three linked, randomised controlled\n                        trials assessing the role, reversibility and mediators of immunomodulation\n                        by chronic infections in the 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