{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:52:49Z","timestamp":1785433969968,"version":"3.56.0"},"reference-count":45,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,1,31]]},"abstract":"<jats:p>\n                    Placental malaria (PM) is a deadly syndrome most frequent and severe in first pregnancies. PM results from accumulation of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    -infected erythrocytes (IE) that express the surface antigen VAR2CSA and bind to chondroitin sulfate A (CSA) in the placenta. Women become PM-resistant over successive pregnancies as they develop anti-adhesion and anti-VAR2CSA antibodies, supporting VAR2CSA as the leading PM-vaccine candidate. However, the first VAR2CSA subunit vaccines failed to induce broadly neutralizing antibody and it is known that naturally acquired antibodies target both variant-specific and conserved epitopes. It is crucial to determine whether effective vaccines will require incorporation of many or only a single VAR2CSA variants. Here, IgG from multigravidae was sequentially purified on five full-length VAR2CSA ectodomain variants, thereby depleting IgG reactivity to each. The five VAR2CSA variants purified ~0.7% of total IgG and yielded both strain-transcending and strain-specific reactivity to VAR2CSA and IE-surface antigen. In two independent antibody purification\/depletion experiments with permutated order of VAR2CSA variants, IgG purified on the first VAR2CSA antigen displayed broad cross-reactivity to both recombinant and native VAR2CSA variants, and inhibited binding of all isolates to CSA. IgG remaining after depletion on all variants showed significantly reduced binding-inhibition activity compared to initial total IgG. These findings demonstrate that a single VAR2CSA ectodomain variant displays conserved epitopes that are targeted by neutralizing (or binding-inhibitory) antibodies shared by multiple parasite strains, including maternal isolates. This suggests that a broadly effective PM-vaccine can be achieved with a limited number of VAR2CSA variants.\n                  <\/jats:p>","DOI":"10.7554\/elife.76264","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T08:00:19Z","timestamp":1643702419000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.76264","source":"Crossref","is-referenced-by-count":24,"title":["A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-7216","authenticated-orcid":true,"given":"Justin YA","family":"Doritchamou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P","family":"Renn","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany","family":"Jenkins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almahamoudou","family":"Mahamar","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, University of Sciences, Techniques, and Technologies of Bamako","place":["Bamako, Mali"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alassane","family":"Dicko","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, University of Sciences, Techniques, and Technologies of Bamako","place":["Bamako, Mali"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Fried","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-5005","authenticated-orcid":true,"given":"Patrick 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