{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:59:26Z","timestamp":1787774366850,"version":"build-2784847793"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI153500,R01AI163188,R01AI180196"],"award-info":[{"award-number":["R01AI153500,R01AI163188,R01AI180196"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:p>\n                    The SARS-CoV-2 pandemic highlighted the potential of mRNA vaccines in rapidly responding to emerging pathogens. However, immunity induced by conventional mRNA vaccines wanes quickly, requiring frequent boosters. Self-amplifying RNA (saRNA) vaccines, which extend antigen expression via self-replication, offer a promising strategy to induce more durable immune responses. In this study, we developed an saRNA vaccine encoding Zika virus (ZIKV) membrane and envelope proteins and evaluated its efficacy in mice. A single vaccination elicited strong humoral and cellular immune responses and reduced viral loads but only for 28 days. By day 84, antibody titers and T cell responses had significantly declined, resulting in reduced efficacy. To address this, we evaluated agonist antibodies targeting the T cell costimulatory molecules OX40 and 4-1BB. Coadministration of agonist antibodies enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses to vaccination, resulting in sustained immunity and reduced viral loads at day 84. Depletion and passive transfer studies verified that long-term antiviral immunity was primarily CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dependent, with minimal contributions from antibody responses. These findings suggest that agonists targeting members of the tumor necrosis receptor superfamily, such as OX40 and 4-1BB, might enhance the durability of saRNA vaccine\u2013induced protection, addressing a key limitation of current mRNA vaccine platforms.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.187405","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T12:00:19Z","timestamp":1743681619000},"source":"Crossref","is-referenced-by-count":7,"title":["Enhanced durability of a Zika virus self-amplifying RNA vaccine through combinatorial OX40 and 4-1BB agonism"],"prefix":"10.1172","volume":"10","author":[{"given":"Hsueh-Han","family":"Lu","sequence":"first","affiliation":[{"name":"Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA."},{"name":"Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California, 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