{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:09Z","timestamp":1787026569858,"version":"build-2736575974"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The durability of vaccine-induced immunity is often limited by waning responses, antigenic drift, and anti-vector immunity, highlighting the need for innovative vaccination strategies. Heterologous prime\u2013boost approaches can help overcome these barriers by exploiting the complementary strengths of distinct platforms. Here, we evaluated a replication-deficient Orf virus-based spike vaccine (ORFV-S) in combination with the licensed Ad26 vector vaccine Jcovden (Ad26.COV2.S), using SARS-CoV-2 model. In a clinically aligned intramuscular immunogenicity screen in mice, Jcovden induced strong early anti-spike antibody responses but showed limited boostability, whereas ORFV-S was highly boost-responsive. Mixed regimens outperformed both homologous schedules. ORFV-S prime followed by Jcovden boost elicited the highest spike-binding antibody titers and vigorous CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses with a dominant Th1 profile. In the reverse regimen, ORFV-S boost improved inhibition across multiple SARS-CoV-2 variants, including immune-evasive strains and indicated qualitative improvements in the response breadth. Together, these findings suggest that sequence-dependent effects allow heterologous schedules to emphasize either cellular or humoral arms of the adaptive response.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1715442","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:23:05Z","timestamp":1763446985000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Heterologous ORFV\u2013Ad26 vaccination broadens antibody breadth and amplifies cellular immunity against SARS-CoV-2 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