{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:23:45Z","timestamp":1790663025287,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["NSERC RGPIN-2017-04179"],"award-info":[{"award-number":["NSERC RGPIN-2017-04179"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Li Ka Shing Institute of Virology at the University of Alberta","award":["2018-2019"],"award-info":[{"award-number":["2018-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>In pregnant women, Plasmodium falciparum-infected red blood cells adhere to the placenta via the parasite protein VAR2CSA. Two vaccine candidates based on VAR2CSA are currently in clinical trials; however, these candidates failed to elicit strain-transcending antibody responses. We previously showed that a cross-reactive monoclonal antibody (3D10) raised against the P. vivax antigen PvDBP targets epitopes in VAR2CSA. We now aim to design a peptide vaccine against VAR2CSA based on the epitope that generated 3D10. We mapped the epitope to subdomain 1 (SD1) of PvDBP and identified a peptide that contained the minimal sequence. However, this peptide did not elicit cross-reactive VAR2CSA antibodies in mice. When tested against a broader, overlapping peptide array spanning SD1, 3D10 in fact recognized a discontinuous epitope consisting of three segments of SD1. These findings presented the challenge to generate this larger structural epitope as a synthetic peptide since it is stabilized by two pairs of disulfide bonds. We overcame this using a synthetic scaffold to conformationally constrain the SD1 peptide and coupled it to keyhole limpet hemocyanin (KLH). The SD1-KLH conjugate elicited antibodies in mice that cross-reacted with VAR2CSA. This strategy successfully recapitulated a discontinuous epitope with a synthetic peptide and represents the first heterologous vaccine candidate against VAR2CSA.<\/jats:p>","DOI":"10.3390\/vaccines8030392","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:08:17Z","timestamp":1595225297000},"page":"392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope"],"prefix":"10.3390","volume":"8","author":[{"given":"Catherine J.","family":"Mitran","sequence":"first","affiliation":[{"name":"School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Higa","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Good","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Southport, Queensland 4215, Australia"},{"name":"Department of Medical Microbiology &amp; Immunology, Faculty of Medicine &amp; Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie K.","family":"Yanow","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada"},{"name":"Department of Medical Microbiology &amp; Immunology, Faculty of Medicine &amp; Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s001090050205","article-title":"Maternal malaria and parasite adhesion","volume":"76","author":"Fried","year":"1998","journal-title":"J. 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