{"doi":"10.1038/s42003-021-02787-7","title":"Allelic variants of full-length VAR2CSA, the placental malaria vaccine candidate, differ in antigenicity and receptor binding affinity","abstract":"Plasmodium falciparum-infected erythrocytes (IE) sequester in the placenta via surface protein VAR2CSA, which binds chondroitin sulfate A (CSA) expressed on the syncytiotrophoblast surface, causing placental malaria (PM) and severe adverse outcomes in mothers and their offspring. VAR2CSA belongs to the PfEMP1 variant surface antigen family; PfEMP1 proteins mediate IE adhesion and facilitate parasite immunoevasion through antigenic variation. Here we produced deglycosylated (native-like) and glycosylated versions of seven recombinant full-length VAR2CSA ectodomains and compared them for antigenicity and adhesiveness. All VAR2CSA recombinants bound CSA with nanomolar affinity, and plasma from Malian pregnant women demonstrated antigen-specific reactivity that increased with gravidity and trimester. However, allelic and glycosylation variants differed in their affinity to CSA and their serum reactivities. Deglycosylated proteins (native-like) showed higher CSA affinity than glycosylated proteins for all variants except NF54. Further, the gravidity-related increase in serum VAR2CSA reactivity (correlates with acquisition of protective immunity) was absent with the deglycosylated form of atypical M200101 VAR2CSA with an extended C-terminal region. Our findings indicate significant inter-allelic differences in adhesion and seroreactivity that may contribute to the heterogeneity of clinical presentations, which could have implications for vaccine design.","journal":"Communications Biology","year":2021,"id":172087,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414017,"name":"Justin Doritchamou","orcid":"0000-0002-4589-7216","position":1,"is_corresponding":false},{"id":708252,"name":"Bergeline C. Nguemwo Tentokam","orcid":null,"position":2,"is_corresponding":false},{"id":414999,"name":"Robert Morrison","orcid":null,"position":3,"is_corresponding":false},{"id":708253,"name":"Matthew V. Cowles","orcid":null,"position":4,"is_corresponding":false},{"id":300350,"name":"Martin Burkhardt","orcid":null,"position":5,"is_corresponding":false},{"id":648117,"name":"Rui Ma","orcid":"0000-0003-0045-2157","position":6,"is_corresponding":false},{"id":448175,"name":"Almahamoudou Mahamar","orcid":null,"position":7,"is_corresponding":false},{"id":565229,"name":"Oumar Attaher","orcid":null,"position":8,"is_corresponding":false},{"id":690948,"name":"Bacary S. Diarra","orcid":"0009-0009-0714-5388","position":9,"is_corresponding":false},{"id":441890,"name":"Moussa Traoré","orcid":"0000-0002-0556-0571","position":10,"is_corresponding":false},{"id":334203,"name":"Alassane Dicko","orcid":"0000-0003-2153-8427","position":11,"is_corresponding":false},{"id":246796,"name":"Niraj H. Tolia","orcid":"0000-0002-2689-1337","position":12,"is_corresponding":false},{"id":285307,"name":"Michal Fried","orcid":"0000-0002-5478-6526","position":13,"is_corresponding":false},{"id":236042,"name":"Patrick E. Duffy","orcid":"0000-0002-4483-5005","position":14,"is_corresponding":false},{"id":569231,"name":"Jonathan P. Renn","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:46:37.150824Z","pmid":"34799664","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":[]}