{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:17:19Z","timestamp":1772187439355,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.17172.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000}}],"reference-count":35,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["211433"],"award-info":[{"award-number":["211433"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:italic>Streptococcus pneumoniae<\/ns3:italic>\n                    is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation.\u00a0 For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi.\n                  <\/ns3:p>\n                  <ns3:p>\n                    This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with\n                    <ns3:italic>S. pneumoniae<\/ns3:italic>\n                    serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage\n                  <\/ns3:p>\n                  <ns3:p>The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population.<\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Trial Registration:<\/ns3:bold>\n                    Pan African Clinical Trial Registry (REF:\n                    <ns3:ext-link xmlns:ns4=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns4:href=\"https:\/\/pactr.samrc.ac.za\/TrialDisplay.aspx?TrialID=12124\">PACTR202008503507113<\/ns3:ext-link>\n                    )\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.17172.2","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T06:25:11Z","timestamp":1655360711000},"page":"240","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-2854","authenticated-orcid":false,"given":"Ben","family":"Morton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-2210","authenticated-orcid":false,"given":"Kondwani","family":"Jambo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-3618","authenticated-orcid":false,"given":"Tarsizio","family":"Chikaonda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2323-3611","authenticated-orcid":false,"given":"Jamie","family":"Rylance","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1242-839X","authenticated-orcid":false,"given":"Marc Y.R.","family":"Henrion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ndaziona Peter","family":"Banda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8440-4219","authenticated-orcid":false,"given":"Edna","family":"Nsomba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-5990","authenticated-orcid":false,"given":"Joel","family":"Gondwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0594-0902","authenticated-orcid":false,"given":"Daniela M.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-1116","authenticated-orcid":false,"given":"Stephen B.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"MARVELS Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1880-2","DOI":"10.1016\/S0140-6736(06)68703-5","article-title":"Pneumococcal vaccination in developing countries.","volume":"367","author":"O Levine","year":"2006","journal-title":"Lancet."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"e744-e57","DOI":"10.1016\/S2214-109X(18)30247-X","article-title":"Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15.","volume":"6","author":"B Wahl","year":"2018","journal-title":"Lancet Glob 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The funder and sponsor have no role in study design; collection, management, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. Neither do they have ultimate authority over any of these activities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}