{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:15:38Z","timestamp":1790806538868,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-006658"],"award-info":[{"award-number":["INV-006658"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"HORIZON EUROPE Framework Programme","doi-asserted-by":"publisher","award":["10079577"],"award-info":[{"award-number":["10079577"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n \n The decline in protective antibody titers and efficacy over time of the circumsporozoite protein (CSP)-based RTS,S\/AS01 and R21\/Matrix-M vaccines highlights the need for improved vaccines. Sporozoite microneme protein essential for cell traversal-1 (SPECT-1) is a conserved\n Plasmodium falciparum<\/jats:italic>\n (\n Pf<\/jats:italic>\n ) antigen that plays a key role in parasite movements while traversing host cells. Targeting SPECT-1 as an addition to the CSP in the same vaccine may enhance immune response and protection.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We engineered a series of recombinant Hepatitis B surface antigen (HBsAg) virus-like particles (VLPs) displaying\n Pf<\/jats:italic>\n SPECT-1 alone or in combination with NANP repeats and C-terminal region of\n Pf<\/jats:italic>\n CSP. These monovalent and bivalent VLP vaccine candidates were evaluated alongside R21 in a prime-boost regimen which was followed by challenge with transgenic\n P. berghei<\/jats:italic>\n parasite expressing the same\n P. falciparum<\/jats:italic>\n antigens. We also assessed the quality of the antibody response following vaccination. Based on the antibody titers and protective efficacy, one bivalent VLP construct was selected for further evaluation with different adjuvant formulations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n All bivalent VLPs formed to display antigenic epitopes that were accessible to antigen-specific antibodies. Bivalent VLPs induced IgG responses against both NANP and\n Pf<\/jats:italic>\n SPECT-1 epitopes, confirming\n in vivo<\/jats:italic>\n co-display of the target antigens. One of the bivalent candidates (N4) provided similar efficacy to R21 in formulation with Matrix-M adjuvant in\n BALB\/c<\/jats:italic>\n mice, whereas addition of\n Pf<\/jats:italic>\n SPECT-1 significantly reduced efficacy of another candidate (N2). NANP-specific IgG response negatively correlated with blood stage parasite load. When N4 was formulated with LMQ or SMNP adjuvants, measured humoral responses or protective efficacy did not improve. Further investigation is needed to determine whether the immune response persists over time.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n Our findings show that\n Pf<\/jats:italic>\n SPECT-1 can be effectively incorporated into the HBsAg VLPs and co-displayed with CSP epitopes without impairing immunogenicity. Although protection was evaluated using transgenic\n P. berghei<\/jats:italic>\n parasites expressing\n P. falciparum<\/jats:italic>\n antigens, the modular HBsAg VLP platform theoretically allows incorporation of antigens from other\n Plasmodium<\/jats:italic>\n species such as\n P. vivax<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1790309","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:45:09Z","timestamp":1778737509000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Bivalent virus-like particles expressing SPECT1 and CSP trigger pre-erythrocytic malaria immunity and protect against transgenic Plasmodium falciparum sporozoite challenge in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Gulbuse","family":"Turan","sequence":"first","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekta","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Truby","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Fedorova","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Polo","family":"Peralta Alvarez","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naif Khalaf","family":"Alharbi","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian V. 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