{"doi":"10.1016/j.immuni.2022.07.015","title":"Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses","abstract":"Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1-2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target.","journal":"Immunity","year":2022,"id":237976,"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":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"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":277649,"name":"Moustafa T. Mabrouk","orcid":"0000-0001-5912-2406","position":1,"is_corresponding":false},{"id":329084,"name":"Kazutoyo Miura","orcid":"0000-0003-4455-2432","position":2,"is_corresponding":false},{"id":225380,"name":"Rashmi Ravichandran","orcid":"0000-0002-2630-7487","position":3,"is_corresponding":false},{"id":552266,"name":"Sally Kephart","orcid":"0000-0002-2285-511X","position":4,"is_corresponding":false},{"id":860977,"name":"Sophia Hailemariam","orcid":"0000-0002-5999-4244","position":5,"is_corresponding":false},{"id":452858,"name":"Thao Pham","orcid":"0000-0002-7667-6897","position":6,"is_corresponding":false},{"id":332932,"name":"Anthony Semesi","orcid":null,"position":7,"is_corresponding":false},{"id":490073,"name":"Iga Kucharska","orcid":"0000-0001-6150-3419","position":8,"is_corresponding":false},{"id":694751,"name":"Prasun Kundu","orcid":"0000-0001-6481-3412","position":9,"is_corresponding":false},{"id":279900,"name":"Wei‐Chiao Huang","orcid":null,"position":10,"is_corresponding":false},{"id":624161,"name":"Max Johnson","orcid":"0000-0002-7470-2094","position":11,"is_corresponding":false},{"id":625025,"name":"Alyssa Blackstone","orcid":null,"position":12,"is_corresponding":false},{"id":225379,"name":"Deleah Pettie","orcid":"0000-0002-5477-7195","position":13,"is_corresponding":false},{"id":225375,"name":"Michael Murphy","orcid":"0000-0002-8438-2653","position":14,"is_corresponding":false},{"id":225381,"name":"John C. 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