{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:08:38Z","timestamp":1792796918072,"version":"4.5.0"},"reference-count":94,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Bioinform Biol Insights"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Plasmodium falciparum is the most fatal species of malaria parasites in humans. Attempts at developing vaccines against the malaria parasites have not been very successful even after the approval of the RTS, S\/AS01 vaccine. There is a continuous need for more effective vaccines including sexual-stage antigens that could block the transmission of malaria parasites between mosquitoes and humans. Low immunogenicity, expression, and stability are some of the challenges of transmission-blocking vaccine (TBV). This study was designed to computationally identify TBV candidates based on fused antigens by combining highly antigenic peptides from prefertilization (Pfs230, Pfs48\/45) and postfertilization (Pfs25, Pfs28) gametocytes. The peptides were selected based on their antigenicity, nonallergenicity, and lack of similarity with the human proteome. Two fused antigens vaccine candidates (FAVCs) were constructed using Flagellin Salmonella enterica (FAVC-FSE) and Cholera toxin B (FAVC-CTB) as adjuvants. The constructs were evaluated for their physicochemical properties, structural stability, immunogenicity, and potential to elicit cross-protection across multiple Plasmodium species. The results yielded antigenic peptides, with antigenicity scores between 0.7589 and 1.1821. The structural analysis of FAVC-FSE and FAVC-CTB showed a Z-score of -6.70 and -4.79, a Ramachandran plot of 96.94% and 94.86% with overall quality of 94.20% and 89.85%, respectively. The FAVCs contained CD8\n                    <jats:sup>+<\/jats:sup>\n                    , CD4\n                    <jats:sup>+<\/jats:sup>\n                    , and linear B-cell epitopes with antigenicity scores between 1.2089 and 2.8623, 0.5663 and 2.4132, and 1.5196 and 2.2212, respectively. Each FAVC generated 6 conformational B-cells. High population coverage values were recorded for the FAVCs. The ability of the FAVCs to trigger immune response was evaluated through an in silico immune stimulation. The low-binding interaction energy that resulted from molecular docking and dynamics simulations showed a strong affinity of FAVCs to Toll-like receptor 5 (TLR5). The results indicate that the FAVC-FSE vaccine candidate is more promising to interrupt P falciparum transmission and provides a baseline for experimental validation.\n                  <\/jats:p>","DOI":"10.1177\/11779322241306215","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T13:50:23Z","timestamp":1741096223000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Computational Development of Transmission-Blocking Vaccine Candidates Based on Fused Antigens of Pre- and Post-fertilization Gametocytes Against\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-8442","authenticated-orcid":false,"given":"Matthew A.","family":"Adeleke","sequence":"first","affiliation":[{"name":"Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"bibr1-11779322241306215","unstructured":"World Health Organization. World Malaria Report 2023, 2023. Accessed October 24, 2024. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2023"},{"key":"bibr2-11779322241306215","unstructured":"World Health Organization. World malaria report 2022, 2022. Accessed December 4, 2024. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2022"},{"key":"bibr3-11779322241306215","unstructured":"World Health Organization. Full evidence report on the RTS, S\/AS01 malaria vaccine, 2021. Accessed December 4, 2024. https:\/\/cdn.who.int\/media\/docs\/default-source\/immunization\/mvip\/full-evidence-report-on-the-rtss-as01-malaria-vaccine-for-sage-mpag-%28sept2021%29.pdf"},{"key":"bibr4-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03006"},{"key":"bibr5-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.668574"},{"key":"bibr6-11779322241306215","unstructured":"University of Oxford. R21\/Matrix-MTM malaria vaccine developed by University of Oxford receives regulatory clearance for use in Ghana, 2023. Accessed September 14, 2024. https:\/\/www.ox.ac.uk\/news\/2023-04-13-r21matrix-m-malaria-vaccine-developed-university-oxford-receives-regulatory"},{"key":"bibr7-11779322241306215","unstructured":"World Health Organization. Malaria Vaccines (RTS, S and R21), 2024. Accessed September 14, 2024. https:\/\/www.who.int\/news-room\/questions-and-answers\/item\/q-a-on-rts-s-malaria-vaccine"},{"key":"bibr8-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-020-0196-3"},{"key":"bibr9-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.945924"},{"key":"bibr10-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33379-6"},{"key":"bibr11-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-24054-3"},{"key":"bibr12-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33236-x"},{"key":"bibr13-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.08.033"},{"key":"bibr14-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00783-y"},{"key":"bibr15-11779322241306215","volume":"15","author":"Lu C","year":"2020","journal-title":"PLoS ONE"},{"key":"bibr16-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01267-12"},{"key":"bibr17-11779322241306215","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6167"},{"key":"bibr18-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apar.2015.04.001"},{"key":"bibr19-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01123-9"},{"key":"bibr20-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01256"},{"key":"bibr21-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-023-06071-x"},{"key":"bibr22-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01998"},{"key":"bibr23-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-4"},{"key":"bibr24-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1101\/gr.092759.109"},{"key":"bibr25-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-S6-S4"},{"key":"bibr26-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/14.8.529"},{"key":"bibr27-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-008-9767-0"},{"key":"bibr28-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-890-0:571"},{"key":"bibr29-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/11.6.681"},{"key":"bibr30-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914677117"},{"key":"bibr31-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt458"},{"key":"bibr32-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm290"},{"key":"bibr33-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560020916"},{"key":"bibr34-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944"},{"key":"bibr35-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae270"},{"key":"bibr36-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx417"},{"key":"bibr37-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-514"},{"key":"bibr38-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009862"},{"key":"bibr39-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762011000900021"},{"key":"bibr40-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2018.1530217"},{"key":"bibr41-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"bibr42-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"bibr43-11779322241306215","author":"Hubbard SJ","year":"1993","journal-title":"Department of Biochemistry and Molecular Biology, University College London"},{"key":"bibr44-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0312-x"},{"key":"bibr45-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1021\/ci200227u"},{"key":"bibr46-11779322241306215","unstructured":"Case DA, Babin V, Berryman JT, et al. AMBER 14. University of California, San Francisco. Accessed December 4, 2024. https:\/\/ambermd.org\/doc12\/Amber14.pdf"},{"key":"bibr47-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"bibr48-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"bibr49-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105375"},{"key":"bibr50-11779322241306215","doi-asserted-by":"crossref","unstructured":"Case DA, Ben-Shalom IY, Brozell SR, et al. AMBER 18, 2018. Accessed December 4, 2024. https:\/\/ambermd.org\/doc12\/Amber18.pdf","DOI":"10.3389\/fnana.2024.1487947"},{"key":"bibr51-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"bibr52-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.08.043"},{"key":"bibr53-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl461"},{"key":"bibr54-11779322241306215","volume-title":"R: a language and environment for statistical computing","author":"Team RC.","year":"2021"},{"key":"bibr55-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-S4-S4"},{"key":"bibr56-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3942"},{"key":"bibr57-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/s12860-020-00334-6"},{"key":"bibr58-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0163-x"},{"key":"bibr59-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215584"},{"key":"bibr60-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/s41182-023-00516-w"},{"key":"bibr61-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00573-19"},{"key":"bibr62-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12060586"},{"key":"bibr63-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.20"},{"key":"bibr64-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-814357-5.00011-8"},{"key":"bibr65-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.230330"},{"key":"bibr66-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01362"},{"key":"bibr67-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.05.006"},{"key":"bibr68-11779322241306215","doi-asserted-by":"crossref","unstructured":"Ahmed MA, Deshmukh GY, Zaidi RH, et al. Identification, mapping, and genetic diversity of novel conserved cross-species epitopes of RhopH2 in plasmodium knowlesi with plasmodium vivax. Front Cell Infect Microbiol. 2022;11:810398. Accessed December 4, 2024. https:\/\/www.frontiersin.org\/journals\/cellular-and-infection-microbiology\/articles\/10.3389\/fcimb.2021.810398","DOI":"10.3389\/fcimb.2021.810398"},{"key":"bibr69-11779322241306215","doi-asserted-by":"crossref","unstructured":"Mitran CJ, Yanow SK. The case for exploiting cross-species epitopes in malaria vaccine design. Front Immunol. 2020;11:335. Accessed December 4, 2024. https:\/\/www.frontiersin.org\/journals\/immunology\/articles\/10.3389\/fimmu.2020.00335","DOI":"10.3389\/fimmu.2020.00335"},{"key":"bibr70-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/s13321-024-00856-7"},{"key":"bibr71-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.5b00103"},{"key":"bibr72-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab295"},{"key":"bibr73-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15956-3"},{"key":"bibr74-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1002\/elps.202000121"},{"key":"bibr75-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2021.104803"},{"key":"bibr76-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2021.104875"},{"key":"bibr77-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2020.06.029"},{"key":"bibr78-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-0918-8"},{"key":"bibr79-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2013.10.005"},{"key":"bibr80-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00106"},{"key":"bibr81-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.884433"},{"key":"bibr82-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1186\/s13029-015-0037-3"},{"key":"bibr83-11779322241306215","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.0518"},{"key":"bibr84-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.05.082"},{"key":"bibr85-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2021.111425"},{"key":"bibr86-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067230"},{"key":"bibr87-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200472109"},{"key":"bibr88-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000770"},{"key":"bibr89-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1038\/322747a0"},{"key":"bibr90-11779322241306215","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.10.5165"},{"key":"bibr91-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.02.004"},{"key":"bibr92-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00263-13"},{"key":"bibr93-11779322241306215","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines3030579"},{"key":"bibr94-11779322241306215","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000273"}],"container-title":["Bioinformatics and Biology Insights"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11779322241306215","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/11779322241306215","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11779322241306215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:56:10Z","timestamp":1777380970000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/11779322241306215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":94,"alternative-id":["10.1177\/11779322241306215"],"URL":"https:\/\/doi.org\/10.1177\/11779322241306215","relation":{},"ISSN":["1177-9322","1177-9322"],"issn-type":[{"value":"1177-9322","type":"print"},{"value":"1177-9322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"article-number":"11779322241306215"}}