{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:28:06Z","timestamp":1780590486907,"version":"3.54.1"},"reference-count":70,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"796","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:p>\n            Messenger RNA (mRNA) has emerged as a highly effective and versatile platform for vaccine delivery. We previously designed a virus-like particle (VLP)\u2013forming\n            <jats:italic toggle=\"yes\">env-gag<\/jats:italic>\n            mRNA vaccine against human immunodeficiency virus\u20131 (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\n            <jats:italic toggle=\"yes\">gag-pol<\/jats:italic>\n            mRNA transcript. Addition of\n            <jats:italic toggle=\"yes\">gag-pol<\/jats:italic>\n            mRNA to an HIV-1\n            <jats:italic toggle=\"yes\">env-gag<\/jats:italic>\n            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.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adt9576","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T02:02:49Z","timestamp":1746064969000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Inclusion of a retroviral protease enhances the immunogenicity of VLP-forming mRNA vaccines against HIV-1 or SARS-CoV-2 in mice"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-8991","authenticated-orcid":true,"given":"Peng","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation and Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, 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