{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:52:36Z","timestamp":1789429956776,"version":"build-2803163510"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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                    We previously demonstrated that vaccination with RSV-Mnull, a prototype single-cycle live vaccine lacking the matrix (M) gene, generated anti-viral serum IgG and memory T cell responses, and reduced challenge virus shedding and pulmonary dysfunction in mice. Here we further characterized the response to RSV-Mnull, and designed and tested second generation Mnull vaccines. In mice, prime-boost vaccination with RSV-Mnull generated pre-fusion (preF) and attachment protein (G) -specific serum IgG and lung IgA, and protected from lung pathology, showing that a single-cycle live vaccine was effective in this model. In an effort to enhance efficacy for future human application, second generation Mnull vaccines were designed, in which nonstructural protein 1 (NS1), a known interferon (IFN) antagonist, was relocated to reduce expression. In addition, the G or F genes were moved to the first genome position (RSV-Mnull\/G1 and RSV-Mnull\/F1 respectively).\n                    <jats:italic>In vitro<\/jats:italic>\n                    , RSV-Mnull\/G1 and RSV-Mnull\/F1 showed reduced NS1 levels and increased IFN-\u03b2 induction, whereas IFN-\u03bb levels were not affected. Viruses with relocated NS1 also displayed enhanced anti-viral state in uninfected cells. RSV-Mnull\/G1 induced higher levels of anti-G serum antibodies (Abs), whereas RSV-Mnull\/F1 increased the ratio of anti-preF:anti-G IgG Abs. RSV-Mnull induced lower levels of lung IgA than wildtype RSV; However, relocation of NS1 increased early IgA induction and restored IgA levels to those seen with wildtype RSV. These findings suggest differences in G and F presentation or processing and Ab induction, and indicate that the genomic location of NS1, G, and F can impact\/improve IgG and IgA levels and timing. All vaccines induced Abs that neutralized RSV\n                    <jats:italic>in vitro<\/jats:italic>\n                    and protected animals against a high challenge dose of wildtype RSV. In terms of protection against lung pathology, we did not see major improvements of RSV-Mnull\/G1 and RSV-Mnull\/F1 over the RSV-Mnull prototype, potentially due to limitations of the model. Nevertheless, RSV-Mnull\/G1 and RSV-Mnull\/F1 elicited high Ab levels against both major antigens, enhanced serum anti-G IgG or lung anti-F IgA levels, and protected mice from lung pathology in spite of single-cycle replication. Thus, the single-cycle approach has potential to be a platform for development of safe and efficacious live RSV vaccines.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1778423","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:05:01Z","timestamp":1775801101000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Next-generation single-cycle respiratory syncytial virus vaccines with increased type I interferon induction yield robust systemic and mucosal responses in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Patil","family":"Basavaraju Nanjegowdu","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University","place":["Stillwater, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeeviya","family":"Murugesan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University","place":["Stillwater, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megolhubino","family":"Terh\u00fcja","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University","place":["Stillwater, OK, United States"]},{"name":"Neovaxsyn, Inc.","place":["Ames, IA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University","place":["Stillwater, OK, United States"]},{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"McElliott","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University","place":["Stillwater, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius G. 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