{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:11:24Z","timestamp":1781107884266,"version":"3.54.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,2,22]]},"abstract":"<jats:p>\n                    In a continuing effort to develop safe and efficacious vaccine and immunotherapeutic vectors, we constructed recombinant vaccinia virus (rVV) vaccines lacking either the B13R (SPI-2) or the B22R (SPI-1) immune-modulating gene and coexpressing IFN-\u03b3. B13R and B22R are nonessential VV immune-modulating genes that have antiapoptotic and antiinflammatory properties with sequence homology to serine protease inhibitors (serpins). IFN-\u03b3 is a cytokine with potent immunoregulatory, antineoplastic, and antiviral properties. We observed that these rVVs with a deletion in a serpin gene and expressing IFN-\u03b3 replicated to high titers in tissue culture yet were avirulent in both immunocompromised and immunocompetent mice with no detectable viral replication in these animals. A single immunization elicited potent humoral, T helper, and cytotoxic T cell immune responses in mice despite the absence of any detectable virus replication\n                    <jats:italic>in vivo<\/jats:italic>\n                    . IFN-\u03b3 coexpression and the inactivation of one or more VV immune-modulating genes provide an optimized method for increasing the safety while maintaining the efficacy of rVV vaccines. This strategy provides a method for developing highly safe and efficacious vaccines for smallpox and other diseases and immunotherapeutic vectors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0409846102","type":"journal-article","created":{"date-parts":[[2005,2,10]],"date-time":"2005-02-10T20:24:39Z","timestamp":1108067079000},"page":"2940-2945","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Vaccinia viruses with a serpin gene deletion and expressing IFN-\u03b3 induce potent immune responses without detectable replication\n                    <i>in vivo<\/i>"],"prefix":"10.1073","volume":"102","author":[{"given":"Fatema A.","family":"Legrand","sequence":"first","affiliation":[{"name":"International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo H.","family":"Verardi","sequence":"additional","affiliation":[{"name":"International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Chan","sequence":"additional","affiliation":[{"name":"International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Peng","sequence":"additional","affiliation":[{"name":"International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A.","family":"Jones","sequence":"additional","affiliation":[{"name":"International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilahun D.","family":"Yilma","sequence":"additional","affiliation":[{"name":"International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,2,10]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11341"},{"key":"e_1_3_2_2_2","first-page":"486","volume":"299","year":"2003","unstructured":"Enserink, M. (2003) Science 299, 486\u2013487.","journal-title":"Science"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/375825"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.123.19.481"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3194758"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.18.8011"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.2.484-491.2002"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0147-9571(03)00019-5"},{"key":"e_1_3_2_9_2","unstructured":"Yilma T. Anderson K. Brechling K. & Moss B. (1987) in Vaccines 87: Modern Approaches to New Vaccines including Prevention of AIDS eds. Chanock R. M. Ginsberg H. Lerner R. & Brown F. (Cold Spring Harbor Lab. Press Woodbury NY) pp. 393\u2013396."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830200123"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.8.3409"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(00)00199-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603252"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8009221"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059742"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.4049\/jimmunol.140.10.3599","volume":"140","year":"1988","unstructured":"Anderson, K. P., Fennie, E. H. & Yilma, T. (1988) J. Immunol. 140, 3599\u20133604.2834443","journal-title":"J. Immunol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/307381a0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.6.2770-2779.2004"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.17.9108"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.11.8999-9010.1999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2981435"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-7974-4_6"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.6.1849-1854.1988"},{"key":"e_1_3_2_24_2","first-page":"16.17.1","volume":"2","year":"1994","unstructured":"Earl, P. L. & Moss, B. (1994) in Current Protocols in Molecular Biology, eds. Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A. & Struhl, K. (Wiley, New York), Vol. 2, pp. 16.17.1\u201316.17.16.","journal-title":"Current Protocols in Molecular Biology"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1385\/0-89603-178-0:217"},{"key":"e_1_3_2_26_2","first-page":"564","volume":"10","year":"1991","unstructured":"Lai, A. C. & Chu, Y. (1991) BioTechniques 10, 564\u2013565.1680352","journal-title":"BioTechniques"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.1.11-18.2001"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.37.2.755-758.1981"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.2144\/97236st07"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/330259a0"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/329545a0"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-1-55"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401165101"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02331"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.15.7713-7723.2002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90321-F"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90752-B"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0409846102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:28:12Z","timestamp":1682987292000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0409846102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2,10]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2005,2,22]]}},"alternative-id":["10.1073\/pnas.0409846102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0409846102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,2,10]]},"assertion":[{"value":"2005-02-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}