{"doi":"10.1126/scitranslmed.adt9576","title":"Inclusion of a retroviral protease enhances the immunogenicity of VLP-forming mRNA vaccines against HIV-1 or SARS-CoV-2 in mice","abstract":"Messenger RNA (mRNA) has emerged as a highly effective and versatile platform for vaccine delivery. We previously designed a virus-like particle (VLP)–forming env-gag mRNA vaccine against human immunodeficiency virus–1 (HIV-1) that elicited envelope-specific neutralizing antibodies and protection from heterologous simian-human immunodeficiency virus (SHIV) infection in rhesus macaques. Here, we introduce a key technological advance to this platform by inclusion of mRNA encoding a retroviral protease to process Gag and produce mature VLPs. Appropriately dosed and timed expression of the protease was achieved using a full-length gag-pol mRNA transcript. Addition of gag-pol mRNA to an HIV-1 env-gag mRNA vaccine resulted in enhanced titers of envelope trimer-binding and neutralizing antibodies in a mouse model. Analogous results were obtained with a hybrid Gag-based, VLP-forming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine expressing an engineered spike protein. Thus, inclusion of a retroviral protease can increase the immunogenicity of Gag-based, VLP-forming mRNA vaccines against human pathogens.","journal":"Science Translational Medicine","year":2025,"id":517363,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1253242,"name":"Mamta Singh","orcid":null,"position":1,"is_corresponding":false},{"id":1250870,"name":"Vada A. Becker","orcid":"0000-0002-7658-7405","position":2,"is_corresponding":false},{"id":829550,"name":"Jacob T. Croft","orcid":"0000-0002-8964-3699","position":3,"is_corresponding":false},{"id":229148,"name":"Yaroslav Tsybovsky","orcid":"0000-0002-2159-5248","position":4,"is_corresponding":false},{"id":1253241,"name":"Vinay Gopan","orcid":null,"position":5,"is_corresponding":false},{"id":1383612,"name":"Yuna Seo","orcid":"0009-0005-3984-2840","position":6,"is_corresponding":false},{"id":412119,"name":"Qingbo Liu","orcid":"0000-0002-1347-6636","position":7,"is_corresponding":false},{"id":627250,"name":"Denise Rogers","orcid":null,"position":8,"is_corresponding":false},{"id":626265,"name":"Huiyi Miao","orcid":"0000-0001-9537-3288","position":9,"is_corresponding":false},{"id":627248,"name":"Yin Lin","orcid":null,"position":10,"is_corresponding":false},{"id":427785,"name":"Daniel C. Rogan","orcid":"0000-0002-9766-4166","position":11,"is_corresponding":false},{"id":1384292,"name":"Courtney Shields","orcid":null,"position":12,"is_corresponding":false},{"id":75378,"name":"Sayda M. Elbashir","orcid":"0000-0001-6250-9679","position":13,"is_corresponding":false},{"id":879379,"name":"Samantha Calabrese","orcid":"0000-0002-8700-3153","position":14,"is_corresponding":false},{"id":105585,"name":"Isabella Renzi","orcid":"0000-0002-2677-7630","position":15,"is_corresponding":false},{"id":1384293,"name":"Vladimir Preznyak","orcid":null,"position":16,"is_corresponding":false},{"id":105594,"name":"Elisabeth Narayanan","orcid":"0000-0001-8836-181X","position":17,"is_corresponding":false},{"id":105606,"name":"Guillaume Stewart-Jones","orcid":"0009-0009-9645-9556","position":18,"is_corresponding":false},{"id":105572,"name":"Sunny Himansu","orcid":"0000-0002-7954-9674","position":19,"is_corresponding":false},{"id":427796,"name":"Mark Connors","orcid":"0000-0002-2108-8705","position":20,"is_corresponding":false},{"id":225389,"name":"Kelly K. 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