{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:04:55Z","timestamp":1780761895516,"version":"3.54.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.22900.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000}}],"reference-count":55,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["733273"],"award-info":[{"award-number":["733273"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    Background Induction of CD8\n                    <ns3:sup>+<\/ns3:sup>\n                    T-cells using viral vectors is a promising strategy in developing effective vaccines against pre-erythrocytic malaria. A recent comparative assessment of candidate antigens using this approach in a mouse model had identified Liver Stage Antigen 1 (LSA1) and Liver Stage Associated Protein 2 (LSAP2) as more protective than TRAP and CSP antigens, which have been the dominant focus of clinical testing. We proposed that combining these within a novel dual antigenic insert (LS2), encoded alongside an orthologous immunogenic domain from invariant chain in ChAdOx1, and the F11 promoter in MVA, could translate to protective clinical efficacy against malaria. Methods We conducted a non-randomised, open-label, dose escalation phase I\/IIa study in UK adults, vaccinating a small lead-in group with ChAdOx1 LS2 5x10\n                    <ns3:sup>9<\/ns3:sup>\n                    vp (group 1; n\u00a0=\u00a03) and subsequently a heterologous prime\u2013boost group with ChAdOx1 LS2 2.5x10\n                    <ns3:sup>10<\/ns3:sup>\n                    vp and MVA LS2 2x10\n                    <ns3:sup>8<\/ns3:sup>\n                    pfu (group 2; n\u00a0=\u00a010). Group 2 volunteers and 6 unvaccinated controls underwent Controlled Human Malaria Infection (CHMI) delivered by mosquito bite and standardized follow-up. Results Vaccination with ChAdOx1 LS2 (both low and full doses) and MVA LS2 were generally well tolerated with solicited symptoms observed similar to previous vectored vaccines and no Severe Adverse Events (SAEs). Immunogenicity of the prime-boost schedule as measured by IFN-\u03b3 ELISpot was high showing median response of 4473 SFC\/10\n                    <ns3:sup>6<\/ns3:sup>\n                    PBMC at the pre-challenge timepoint, covering a broad range of potential determinants. All vaccinated volunteers became infected with malaria during CHMI with a median time to diagnosis of 13\u00a0days compared to 13.25\u00a0days in controls. Conclusions Though this study further indicates ChAd\/MVA as a safe, highly effective platform for driving CD8\n                    <ns3:sup>+<\/ns3:sup>\n                    responses specific to liver-stage malaria antigens, the promise of LSA1 and LSAP2 as potential candidates shown preclinically has not translated to protection from infection in humans. Clinical Trial Registration ClinicalTrials.gov (Ref: NCT03203421), date of registration, 3\n                    <ns3:sup>rd<\/ns3:sup>\n                    July 2017.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.22900.2","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T10:34:07Z","timestamp":1775471647000},"page":"734","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Phase I\/IIa study to assess the safety, immunogenicity and efficacy of ChAdOx1-MVA vectored vaccines expressing a novel liver-stage malaria dual antigen LS2 by sporozoite challenge in malaria-na\u00efve adults"],"prefix":"10.12688","volume":"9","author":[{"given":"Daniel","family":"Silman","sequence":"first","affiliation":[{"name":"Jenner Institute, Nuffield Department of Medicine, NIHR Biomedical Research Centre Oxford England OX3 7DQ University of Oxford Nuffield Department of 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:34:11Z","timestamp":1776443651000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":55,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.22900.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/wellcomeopenres.22900.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.28984.r152696","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.28984.r152696","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.28984.r152824","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.25216.r118989, Anneth Tumbo, Ifakara Health Institute, Ifakara, 19 Mar 2025, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v1#referee-response-118989","order":0,"name":"referee-response-118989","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Katie Ewer<\/b>; \n<i>Posted: 18 Mar 2026<\/i>; We thank the reviewer for their positive feedback. Regarding the comment on further antibody profiling, in light of the lack of protection afforded by the vaccine, we did not undertake futher immunological studies.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2#referee-comment-6473","order":1,"name":"referee-comment-6473","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.28984.r152696, Helena Nunes Caba\u00e7o, Gulbenkian Institute for Molecular Medicine, Lisbon, 09 Apr 2026, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-734\/v2#referee-response-152696","order":2,"name":"referee-response-152696","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The study was funded through the European Commission under the Horizon2020 programme. This was part of OPTIMALVAX Consortium, Grant Agreement No. 733273. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"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"}]}}