{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:50:27Z","timestamp":1790905827320,"version":"4.1.0"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the VV-specific T-cell response and how this compares to the immune response to the foreign gene(s) expressed by the rVV. To address this issue, we quantitated the T-cell responses to both the viral vector and the insert following the infection of mice with VV expressing a cytotoxic T lymphocyte (CTL) epitope (NP118-126) from lymphocytic choriomeningitis virus (LCMV). The LCMV epitope-specific response was quantitated by intracellular cytokine staining after stimulation with the specific peptide. To analyze the total VV-specific response, we developed a simple intracellular cytokine staining assay using VV-infected major histocompatibility complex class I and II matched cells as stimulators. Using this approach, we made the following determinations. (i) VV-NP118 induced potent and long-lasting CD8 and CD4 T-cell responses to the vector; at the peak of the response (\u223c1 week), there were \u223c10<jats:sup>7<\/jats:sup>VV-specific CD8 T cells (25% of the CD8 T cells) and \u223c10<jats:sup>6<\/jats:sup>VV-specific CD4 T cells (\u223c5% of the CD4 T cells) in the spleen. These numbers decreased to \u223c5 \u00d7 10<jats:sup>5<\/jats:sup>CD8 T cells (\u223c5% frequency) and \u223c10<jats:sup>5<\/jats:sup>CD4 T cells (\u223c0.5% frequency), respectively, by day 30 and were then stably maintained at these levels for &gt;300 days. The size of this VV-specific T-cell response was comparable to that of the T-cell response induced following an acute LCMV infection. (ii) VV-specific CD8 and CD4 T cells were capable of producing gamma interferon (IFN-\u03b3), tumor necrosis factor alpha (TNF-\u03b1), and interleukin-2; all cells were able to make IFN-\u03b3, a subset produced both IFN-\u03b3 and TNF-\u03b1, and another subset produced all three cytokines. (iii) The CD8 T-cell response to the foreign gene (LCMV NP118-126 epitope) was coordinately regulated with the response to the vector during all three phases (expansion, contraction, and memory) of the T-cell response. The total number of CD8 T cells responding to NP118-126 were \u223c20- to 30-fold lower than the number responding to the VV vector (\u223c1% at the peak and 0.2% in memory). This study provides a better understanding of T-cell immunity induced by VV-based vaccines, and in addition, the technique described in the study can be readily extended to other viral vectors to determine the ratio of the T-cell response to the insert versus the vector. This information will be useful in optimizing prime-boost regimens for vaccination.<\/jats:p>","DOI":"10.1128\/jvi.76.7.3329-3337.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:58:35Z","timestamp":1027763915000},"page":"3329-3337","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":147,"title":["Recombinant Vaccinia Virus-Induced T-Cell Immunity: Quantitation of the Response to the Virus Vector and the Foreign Epitope"],"prefix":"10.1128","volume":"76","author":[{"given":"Laurie E.","family":"Harrington","sequence":"first","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert van der","family":"Most","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Lindsay","family":"Whitton","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01311113"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-1669(97)80031-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni727"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.3.1538-1544.1993"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00226-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.11.5611-5616.1990"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199905070-00005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/369648a0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.12.7340-7349.1993"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.4.1043"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200011100-00034"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.2.923-933.2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.16.7651-7655.2000"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01612-1"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.2460\/ajvr.1994.55.09.1250","volume":"55","year":"1994","unstructured":"Schaffner, J. W., U. Dittmer, A. Otteken, C. Coulibaly, W. Bodemer, G. Voss, and G. Hunsmann. 1994. Comparison of humoral immunity and induction of proliferating T lymphocytes in vaccinia virus-infected rabbits and rhesus macaques. Am. J. Vet. Res. 55 : 1250-1255.","journal-title":"Am. J. Vet. Res."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.208"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10847"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.9.4429-4432.2000"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.1.348-352.1993"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"5526","DOI":"10.4049\/jimmunol.163.10.5526","volume":"163","year":"1999","unstructured":"Zajac, A. J., R. E. Vance, W. Held, D. J. Sourdive, J. D. Altman, D. H. Raulet, and R. Ahmed. 1999. Impaired anti-viral T cell responses due to expression of the Ly49A inhibitory receptor. J. Immunol. 163 : 5526-5534.","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0792"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.76.7.3329-3337.2002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.76.7.3329-3337.2002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T20:03:02Z","timestamp":1733688182000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.76.7.3329-3337.2002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4]]},"references-count":22,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2002,4]]}},"alternative-id":["10.1128\/JVI.76.7.3329-3337.2002"],"URL":"https:\/\/doi.org\/10.1128\/jvi.76.7.3329-3337.2002","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4]]},"assertion":[{"value":"2001-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}