{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:54:01Z","timestamp":1758707641498},"reference-count":55,"publisher":"American Society for Microbiology","issue":"18","license":[{"start":{"date-parts":[[2006,9,15]],"date-time":"2006-09-15T00:00:00Z","timestamp":1158278400000},"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":[[2006,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Natural transmission of human immunodeficiency virus (HIV) occurs at mucosal surfaces. During acute infection, intestinal and other mucosae are preferential sites of virus replication and rapidly become depleted of CD4<jats:sup>+<\/jats:sup>T cells. Therefore, mucosal immunity may be critical to control both initial infection and the massive early spread of virus. An attenuated<jats:sc>d<\/jats:sc>-alanine-requiring strain of the oral intracellular microorganism<jats:italic>Listeria monocytogenes<\/jats:italic>expressing HIV type 1<jats:italic>gag<\/jats:italic>was shown to induce protective cell-mediated immunity in mice against viruses that express HIV<jats:italic>gag<\/jats:italic>when immunization occurs in the presence of a transient supply of<jats:sc>d<\/jats:sc>-alanine. In this study, we examined the efficacy of new attenuated strains that are able to synthesize<jats:sc>d<\/jats:sc>-alanine from a heterologous<jats:italic>dal<\/jats:italic>gene tightly regulated by an<jats:italic>actA<\/jats:italic>-promoted resolvase recombination system. In the absence of<jats:sc>d<\/jats:sc>-alanine, Gag-specific cytotoxic T lymphocytes (CTLs) were induced systemically after intravenous immunization, and one strain, Lmdd-gag\/pARS, induced strong dose-dependent Gag-specific CTLs after oral immunization. A significant level of Gag-specific CD8<jats:sup>+<\/jats:sup>T cells was induced in the mucosal-associated lymphoid tissues (MALTs). Upon intravaginal challenge of these orally immunized mice with recombinant vaccinia virus (rVV) expressing HIV<jats:italic>gag<\/jats:italic>, gamma interferon- and tumor necrosis factor alpha-secreting Gag-specific CD8<jats:sup>+<\/jats:sup>T cells were dramatically increased in the spleen and MALTs. Oral immunization with Lmdd-gag\/pARS led to complete protection against vaginal challenge by a homologous clade B<jats:italic>gag<\/jats:italic>-expressing rVV. In addition, strong cross-clade protection was seen against clades A and C and partial protection against clade G<jats:italic>gag<\/jats:italic>-expressing rVV. These results suggest that Lmdd-gag\/pARS may be considered as a novel vaccine candidate for use against HIV\/AIDS.<\/jats:p>","DOI":"10.1128\/jvi.00894-06","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T22:59:30Z","timestamp":1156892370000},"page":"8880-8890","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Vaginal Protection and Immunity after Oral Immunization of Mice with a Novel Vaccine Strain of<i>Listeria monocytogenes<\/i>Expressing Human Immunodeficiency Virus Type 1<i>gag<\/i>"],"prefix":"10.1128","volume":"80","author":[{"given":"Xinyan","family":"Zhao","sequence":"first","affiliation":[{"name":"University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, Pennsylvania 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, Pennsylvania 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongxia","family":"Li","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, Pennsylvania 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred R.","family":"Frankel","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, Pennsylvania 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4102"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.253-258.1999"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.12.026"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1987.tb00521.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040874"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1276"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406035101"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80540-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.2.834"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/428450"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/344232"},{"key":"e_1_3_2_13_2","first-page":"476","volume":"55","year":"1991","unstructured":"Farber, J. M., and P. I. Peterkin. 1991. Listeria monocytogenes, a food-borne pathogen. Microbiol. Mol. Biol. Rev.55:476-511.","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/420833"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.4.1396"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"4775","DOI":"10.4049\/jimmunol.155.10.4775","volume":"155","year":"1995","unstructured":"Frankel, F. R., S. Hedge, J. Lieberman, and Y. Paterson. 1995. Induction of cell-mediated immune responses to human immunodeficiency virus type 1 Gag protein by using Listeria monocytogenes as a live vaccine vector. J. Immunol.155:4775-4782.","journal-title":"J. Immunol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.21.9987-9993.2000"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.5.797"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1338"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.21.11708-11717.2003"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6471"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00272-7"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(96)00188-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8467-8474.1997"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.1.393-400.2005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/75843"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.001021"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.9.1275"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03513"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.5065-5073.2005"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.4049\/jimmunol.161.6.2985","volume":"161","year":"1998","unstructured":"Mata, M., P. J. Travers, Q. Liu, F. R. Frankel, and Y. Paterson. 1998. The MHC class I-restricted immune response to HIV-gag in BALB\/c mice selects a single epitope that does not have a predictable MHC-binding motif and binds to Kd through interactions between a glutamine at P3 and pocket D. J. Immunol.161:2985-2993.","journal-title":"J. Immunol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03501"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000184858.16447.04"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041196"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2014-2021.2004"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1777"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270637"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/353852a0"},{"key":"e_1_3_2_39_2","first-page":"4776","volume":"55","year":"1995","unstructured":"Pan, Z.-K., G. Ikonomidis, D. Pardoll, and Y. Paterson. 1995. Regression of established tumors in mice mediated by the oral administration of a recombinant Listeria monocytogenes vaccine. Cancer Res.55:4776-4779.","journal-title":"Cancer Res."},{"key":"e_1_3_2_40_2","first-page":"5264","volume":"59","year":"1999","unstructured":"Pan, Z. K., L. M. Weiskirch, and Y. Paterson. 1999. Regression of established B16F10 melanoma with a recombinant Listeria monocytogenes vaccine. Cancer Res.59:5264-5269.","journal-title":"Cancer Res."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(90)90479-B"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.10.5176"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3402"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.4.1263-1267.1992"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01669.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.2.918-922.2002"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.6.2786-2791.2001"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80946-0"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3987"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.1.420"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.4.1597"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1244"},{"key":"e_1_3_2_53_2","unstructured":"UNAIDS. 2005. AIDS epidemic update\u20142005 December. UNAIDS Geneva Switzerland."},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00081-5"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021109"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5789-5798.2005"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00894-06","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00894-06","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T06:35:07Z","timestamp":1707201307000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00894-06"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,15]]},"references-count":55,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2006,9,15]]}},"alternative-id":["10.1128\/JVI.00894-06"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00894-06","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,15]]},"assertion":[{"value":"2006-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-06-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}