{"doi":"10.7554/elife.76264","title":"A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates","abstract":"-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.","journal":"eLife","year":2022,"id":250495,"datarank":0.8236396319048953,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.32926410200424583,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.32926410200424583,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":20,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01168271"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":569231,"name":"Jonathan P. Renn","orcid":null,"position":1,"is_corresponding":false},{"id":569230,"name":"Bethany J. Jenkins","orcid":null,"position":2,"is_corresponding":false},{"id":448175,"name":"Almahamoudou Mahamar","orcid":null,"position":3,"is_corresponding":false},{"id":334203,"name":"Alassane Dicko","orcid":"0000-0003-2153-8427","position":4,"is_corresponding":false},{"id":285307,"name":"Michal Fried","orcid":"0000-0002-5478-6526","position":5,"is_corresponding":false},{"id":236042,"name":"Patrick E. Duffy","orcid":"0000-0002-4483-5005","position":6,"is_corresponding":false},{"id":414017,"name":"Justin Doritchamou","orcid":"0000-0002-4589-7216","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T00:24:32.960657Z","pmid":"35103596","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}