{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:40:28Z","timestamp":1787586028764,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2014,10,17]],"date-time":"2014-10-17T00:00:00Z","timestamp":1413504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister\/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8\u0394. LC16m8\u2206 is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8\u2206 is &gt;500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8\u2206, which expresses the SIV gag gene, also induced anti-Gag CD8+ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8\u2206 expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8+ T-cells. Thus, the safety and efficacy of LC16m8\u2206 mean that it represents an outstanding platform for the development of human vaccine vectors.<\/jats:p>","DOI":"10.3390\/vaccines2040755","type":"journal-article","created":{"date-parts":[[2014,10,17]],"date-time":"2014-10-17T10:27:19Z","timestamp":1413541639000},"page":"755-771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Vaccinia Virus LC16m8\u2206 as a Vaccine Vector for  Clinical Applications"],"prefix":"10.3390","volume":"2","author":[{"given":"Minoru","family":"Kidokoro","sequence":"first","affiliation":[{"name":"Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisatoshi","family":"Shida","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,10,17]]},"reference":[{"key":"ref_1","unstructured":"Fenner, F., Henderson, D.A., Arita, I., Jezek, Z., Ladnyi, I.D., and Organization, W.H. (1988). Smallpox and Its Eradication, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1093\/infdis\/142.4.636","article-title":"A reality in our time\u2014Certification of the global eradication of smallpox","volume":"142","author":"Wehrle","year":"1980","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1001\/jama.281.22.2127","article-title":"Smallpox as a biological weapon: Medical and public health management. Working group on civilian biodefense","volume":"281","author":"Henderson","year":"1999","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1056\/NEJMoa032299","article-title":"The detection of monkeypox in humans in the western hemisphere","volume":"350","author":"Reed","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"The Centers for Disease Control and Prevention (2003). Multistate outbreak of monkeypox\u2014Illinois, indiana, and wisconsin, 2003. JAMA, 290, 30\u201331.","DOI":"10.1001\/jama.290.1.30"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2009.06.006","article-title":"Vaccinia virus vaccines: Past, present and future","volume":"84","author":"Jacobs","year":"2009","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1586\/erv.11.79","article-title":"Vaccinia viruses: Vaccines against smallpox and vectors against infectious diseases and tumors","volume":"10","author":"Walsh","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"961","DOI":"10.4161\/hv.21080","article-title":"A vaccinia virus renaissance: New vaccine and immunotherapeutic uses after smallpox eradication","volume":"8","author":"Verardi","year":"2012","journal-title":"Human Vaccines Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1001\/jama.294.21.2734","article-title":"Adverse events associated with smallpox vaccination in the United States, January\u2013October 2003","volume":"294","author":"Casey","year":"2005","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1001\/jama.294.21.2744","article-title":"Neurologic adverse events associated with smallpox vaccination in the united states, 2002\u20132004","volume":"294","author":"Sejvar","year":"2005","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3201\/eid1107.050277","article-title":"Adventitious agents and smallpox vaccine in strategic national stockpile","volume":"11","author":"Murphy","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/nm916","article-title":"Clonal vaccinia virus grown in cell culture as a new smallpox vaccine","volume":"9","author":"Weltzin","year":"2003","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.vaccine.2008.11.079","article-title":"Comparison of the safety and immunogenicity of ACAM1000, ACAM2000 and Dryvax\u00ae in healthy vaccinia-naive adults","volume":"27","author":"Frey","year":"2009","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ijid.2004.09.002","article-title":"Acam2000 clonal vero cell culture vaccinia virus (New York city board of health strain)\u2014A second-generation smallpox vaccine for biological defense","volume":"8","author":"Monath","year":"2004","journal-title":"Int. J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0140-6736(05)70234-8","article-title":"Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: A blind, single-centre, randomised controlled trial","volume":"365","author":"Greenberg","year":"2005","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7845","DOI":"10.1128\/JVI.79.12.7845-7851.2005","article-title":"Modified vaccinia virus ankara protects macaques against respiratory challenge with monkeypox virus","volume":"79","author":"Stittelaar","year":"2005","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1055\/s-0028-1108143","article-title":"MVA vaccination against smallpox: Clinical tests with an attenuated live vaccinia virus strain (MVA)","volume":"99","author":"Stickl","year":"1974","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_18","first-page":"375","article-title":"The smallpox vaccination strain MVA: Marker, genetic structure, experience gained with the parenteral vaccination and behavior in Organisms with a debilitated defence mechanism","volume":"167","author":"Mayr","year":"1978","journal-title":"Zentralbl. Bakteriol. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/2151187a0","article-title":"Immunogenicity of an attenuated strain of vaccinia virus on rabbits and monkeys","volume":"215","author":"Kitamura","year":"1967","journal-title":"Nature"},{"key":"ref_20","first-page":"229","article-title":"Special edition future of smallpox vaccination: Everything about attenuated smallpox vaccines. Basics of new attenuated smallpox vaccine strain LC16m8","volume":"3","author":"Hashizume","year":"1975","journal-title":"Rinshotouirusu"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF01314664","article-title":"Comparative studies of several vaccinia virus strains by intrathalamic inoculation into cynomolgus monkeys","volume":"53","author":"Morita","year":"1977","journal-title":"Arch. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1348-0421.1977.tb00306.x","article-title":"A comparison of neurovirulence of vaccinia virus by intrathalamic and\/or intracisternal inoculations into cynomolgus monkeys","volume":"21","author":"Morita","year":"1977","journal-title":"Microbiol. Immunol."},{"key":"ref_23","unstructured":"Hashizume, S., Yoshizawa, H., Morita, M., and Suzuki, K. (1985). Properties of Attenuated Mutant of Vaccinia Virus, LC16m8, Derived from Lister Strain, Elsevier Science Publishing Co. Inc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1099\/0022-1317-72-5-1031","article-title":"Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence","volume":"72","author":"Meyer","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1006\/viro.1998.9397","article-title":"Marker rescue of the host range restriction defects of modified vaccinia virus Ankara","volume":"251","author":"Wyatt","year":"1998","journal-title":"Virology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/0042-6822(90)90296-4","article-title":"Vaccinia virus host range genes","volume":"179","author":"Perkus","year":"1990","journal-title":"Virology"},{"key":"ref_27","first-page":"283","article-title":"An attenuated strain of vaccinia virus (MVA). Successful intramuscular immunization against vaccinia and variola","volume":"230","author":"Hanichen","year":"1975","journal-title":"Zentralbl. Bakteriol. Orig. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0147-9571(03)00025-0","article-title":"Smallpox vaccination and bioterrorism with pox viruses","volume":"26","author":"Mayr","year":"2003","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.vaccine.2005.11.022","article-title":"Safety and immunogenicity of imvamune, a promising candidate as a third generation smallpox vaccine","volume":"24","author":"Vollmar","year":"2006","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.1016\/j.vaccine.2007.10.017","article-title":"Clinical and immunologic responses to multiple doses of imvamune (modified vaccinia Ankara) followed by dryvax challenge","volume":"25","author":"Frey","year":"2007","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1586\/14760584.8.1.13","article-title":"Imvamune: Modified vaccinia Ankara strain as an attenuated smallpox vaccine","volume":"8","author":"Kennedy","year":"2009","journal-title":"Expert Rev. Vaccines"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1086\/651560","article-title":"Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax","volume":"201","author":"Seaman","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1086\/651561","article-title":"Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): Effect of dose and route of administration","volume":"201","author":"Wilck","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1073\/pnas.0406671102","article-title":"Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8","volume":"102","author":"Kidokoro","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.virol.2005.06.002","article-title":"Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine dryvax in a mouse model","volume":"339","author":"Meseda","year":"2005","journal-title":"Virology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.1073\/pnas.0401165101","article-title":"Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge","volume":"101","author":"Wyatt","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1006\/viro.2002.1622","article-title":"Structural analysis of vaccinia virus Dis strain: Application as a new replication-deficient viral vector","volume":"302","author":"Ishii","year":"2002","journal-title":"Virology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7009","DOI":"10.1016\/j.vaccine.2006.03.087","article-title":"LC16m8: An attenuated smallpox vaccine","volume":"24","author":"Kenner","year":"2006","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1542\/peds.42.6.980","article-title":"Smallpox vaccination of eczema patients with a strain of attenuated live vaccinia (CVI-78)","volume":"42","author":"Kempe","year":"1968","journal-title":"Pediatrics"},{"key":"ref_40","first-page":"225","article-title":"Vaccination research groups research report: Ministry of health and welfare special research: Postvaccination side effects and research regarding treatment of complications","volume":"3","author":"Yamaguchi","year":"1975","journal-title":"Rinsho Uirusu Clin. Virus"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0042-6822(92)90752-B","article-title":"NYVAC: A highly attenuated strain of vaccinia virus","volume":"188","author":"Tartaglia","year":"1992","journal-title":"Virology"},{"key":"ref_42","first-page":"65","article-title":"Safe and effective poxvirus vectors\u2014NYVAC and ALVAC","volume":"82","author":"Paoletti","year":"1994","journal-title":"Dev. Biol. Stand."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1128\/jvi.71.7.4997-5002.1997","article-title":"Construction of a vaccinia virus deficient in the essential DNA repair enzyme uracil DNA glycosylase by a complementing cell line","volume":"71","author":"Holzer","year":"1997","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1128\/JVI.73.6.4536-4542.1999","article-title":"Highly efficient induction of protective immunity by a vaccinia virus vector defective in late gene expression","volume":"73","author":"Holzer","year":"1999","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.1128\/JVI.76.15.7713-7723.2002","article-title":"Immunogenicity and safety of defective vaccinia virus lister: Comparison with modified vaccinia virus Ankara","volume":"76","author":"Ober","year":"2002","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.virol.2005.06.043","article-title":"The nonreplicating smallpox candidate vaccines defective vaccinia lister (DVV-l) and modified vaccinia Ankara (MVA) elicit robust long-term protection","volume":"341","author":"Coulibaly","year":"2005","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6033","DOI":"10.1128\/JVI.02108-05","article-title":"Cellular and biochemical differences between two attenuated poxvirus vaccine candidates (MVA and NYVAC) and role of the C7L gene","volume":"80","author":"Najera","year":"2006","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.vaccine.2007.12.059","article-title":"Short- and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine","volume":"26","author":"Drillien","year":"2008","journal-title":"Vaccine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/0042-6822(91)90480-Y","article-title":"Regulation of plaque size and host range by a vaccinia virus gene related to complement system proteins","volume":"181","author":"Funahashi","year":"1991","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1099\/0022-1317-83-12-2915","article-title":"The formation and function of extracellular enveloped vaccinia virus","volume":"83","author":"Smith","year":"2002","journal-title":"J. Gen. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1128\/jvi.68.1.130-147.1994","article-title":"Assembly of vaccinia virus: The second wrapping cisterna is derived from the trans golgi network","volume":"68","author":"Schmelz","year":"1994","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1083\/jcb.200104124","article-title":"Vaccinia virus utilizes microtubules for movement to the cell surface","volume":"154","author":"Hollinshead","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1038\/ncb1101-992","article-title":"Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus","volume":"3","author":"Rietdorf","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1128\/JVI.75.10.4802-4813.2001","article-title":"Visualization of intracellular movement of vaccinia virus virions containing a green fluorescent protein-B5R membrane protein chimera","volume":"75","author":"Ward","year":"2001","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12266","DOI":"10.1128\/JVI.77.22.12266-12275.2003","article-title":"Mutations in the vaccinia virus A33R and B5R envelope proteins that enhance release of extracellular virions and eliminate formation of actin-containing microvilli without preventing tyrosine phosphorylation of the A36R protein","volume":"77","author":"Katz","year":"2003","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1126\/science.1101509","article-title":"Src mediates a switch from microtubule- to actin-based motility of vaccinia virus","volume":"306","author":"Newsome","year":"2004","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1099\/0022-1317-66-3-643","article-title":"Extracellular release of enveloped vaccinia virus from mouse nasal epithelial cells in vivo","volume":"66","author":"Payne","year":"1985","journal-title":"J. Gen. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1006\/viro.1998.9516","article-title":"Neutralizing and protective antibodies directed against vaccinia virus envelope antigens","volume":"254","author":"Galmiche","year":"1999","journal-title":"Virology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0042-6822(02)00038-7","article-title":"Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates","volume":"306","author":"Hooper","year":"2003","journal-title":"Virology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1016\/j.vaccine.2004.02.034","article-title":"Differential efficacy of vaccinia virus envelope proteins administered by DNA immunisation in protection of BALB\/c mice from a lethal intranasal poxvirus challenge","volume":"22","author":"Pulford","year":"2004","journal-title":"Vaccine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1128\/JVI.78.9.4433-4443.2004","article-title":"Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox","volume":"78","author":"Hooper","year":"2004","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1099\/0022-1317-71-11-2761","article-title":"Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route","volume":"71","author":"Williamson","year":"1990","journal-title":"J. Gen. Virol."},{"key":"ref_63","unstructured":"Kidokoro, M.S.S., Ami, Y., Suzaki, Y., Nagata, N., Iwata, N., Hasegawa, H., Ogata, M., Fukushi, H., Mizutani, T., and Shida, H. (2006, January 19\u201321). Protective effects of improved smalpox vaccine LC16m8\u2206 against a lethal monkeypox challenge in cynomolgus monkeys. Proceedings of the 54th Annual Meeting of the Japanese Society for Virology, Nagoya, Japan."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1006\/viro.1999.0096","article-title":"DNA vaccination with vaccinia virus L1R and A33R genes protects mice against a lethal poxvirus challenge","volume":"266","author":"Hooper","year":"2000","journal-title":"Virology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.1128\/JVI.00353-08","article-title":"Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice","volume":"82","author":"Kaufman","year":"2008","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1128\/JVI.02642-05","article-title":"LC16m8, a highly attenuated vaccinia virus vaccine lacking expression of the membrane protein B5R, protects monkeys from monkeypox","volume":"80","author":"Saijo","year":"2006","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11873","DOI":"10.1128\/JVI.79.18.11873-11891.2005","article-title":"An attenuated LC16m8 smallpox vaccine: Analysis of full-genome sequence and induction of immune protection","volume":"79","author":"Morikawa","year":"2005","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1128\/JVI.02244-07","article-title":"Redundancy and plasticity of neutralizing antibody responses are cornerstone attributes of the human immune response to the smallpox vaccine","volume":"82","author":"Benhnia","year":"2008","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1128\/JVI.02089-12","article-title":"Humoral immunity to smallpox vaccines and monkeypox virus challenge: Proteomic assessment and clinical correlations","volume":"87","author":"Townsend","year":"2013","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.vaccine.2008.12.035","article-title":"The heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays","volume":"27","author":"Wollenick","year":"2009","journal-title":"Vaccine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1126\/science.2047875","article-title":"Vaccinia virus: A tool for research and vaccine development","volume":"252","author":"Moss","year":"1991","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1749-6632.1995.tb44454.x","article-title":"Live attenuated vaccinia and other poxviruses as delivery systems: Public health issues","volume":"754","author":"Perkus","year":"1995","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/QAI.0b013e3181354bd7","article-title":"A phase 1\/2 comparative vaccine trial of the safety and immunogenicity of a CRF01_AE (subtype E) candidate vaccine: ALVAC-HIV (vCP1521) prime with oligomeric gp160 (92TH023\/LAI-DID) or bivalent gp120 (CM235\/SF2) boost","volume":"46","author":"Thongcharoen","year":"2007","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"15547","DOI":"10.1128\/JVI.79.24.15547-15555.2005","article-title":"Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag","volume":"79","author":"Casimiro","year":"2005","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"13348","DOI":"10.1128\/JVI.77.24.13348-13360.2003","article-title":"Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239","volume":"77","author":"Vogel","year":"2003","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8161","DOI":"10.1128\/JVI.00620-08","article-title":"DNA gag\/adenovirus type 5 (Ad5) gag and Ad5 gag\/Ad5 gag vaccines induce distinct T-cell response profiles","volume":"82","author":"Cox","year":"2008","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.1128\/JVI.80.10.4717-4728.2006","article-title":"Induction of multifunctional human immunodeficiency virus type 1 (HIV-1)-specific T cells capable of proliferation in healthy subjects by using a prime-boost regimen of DNA- and modified vaccinia virus ankara-vectored vaccines expressing HIV-1 gag coupled to CD8+ T-cell epitopes","volume":"80","author":"Goonetilleke","year":"2006","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1084\/jem.20071331","article-title":"An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses","volume":"205","author":"Harari","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S0140-6736(13)60177-4","article-title":"Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: A randomised, placebo-controlled phase 2b trial","volume":"381","author":"Tameris","year":"2013","journal-title":"Lancet"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.1152622","article-title":"Toward an AIDS vaccine","volume":"320","author":"Walker","year":"2008","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.vaccine.2006.08.039","article-title":"SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus","volume":"25","author":"Kitabatake","year":"2007","journal-title":"Vaccine"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.virol.2006.11.020","article-title":"B5-deficient vaccinia virus as a vaccine vector for the expression of a foreign antigen in vaccinia immune animals","volume":"361","author":"Viner","year":"2007","journal-title":"Virology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF01379134","article-title":"Constructions of vaccinia virus A-type inclusion body protein, tandemly repeated mutant 7.5 kDa protein, and hemagglutinin gene promoters support high levels of expression","volume":"138","author":"Jin","year":"1994","journal-title":"Arch. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/S1286-4579(02)01627-1","article-title":"Large-scale preparation of biologically active measles virus haemagglutinin expressed by attenuated vaccinia virus vectors","volume":"4","author":"Kidokoro","year":"2002","journal-title":"Microbes Infect."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1099\/0022-1317-69-1-35","article-title":"Cloning and characterization of the gene encoding the major protein of the A-type inclusion body of cowpox virus","volume":"69","author":"Funahashi","year":"1988","journal-title":"J. Gen. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.vaccine.2008.12.015","article-title":"Immunogenicity of newly constructed attenuated vaccinia strain LC16m8delta that expresses SIV gag protein","volume":"27","author":"Suzuki","year":"2009","journal-title":"Vaccine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nm1520","article-title":"CD8+ T-cell responses to different HIV proteins have discordant associations with viral load","volume":"13","author":"Kiepiela","year":"2007","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1084\/jem.20040432","article-title":"Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial","volume":"199","author":"Matano","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1111\/j.1348-0421.2006.tb03867.x","article-title":"Recombinant vaccinia Dis expressing simian immunodeficiency virus gag and pol in mammalian cells induces efficient cellular immunity as a safe immunodeficiency virus vaccine candidate","volume":"50","author":"Okamura","year":"2006","journal-title":"Microbiol. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1128\/jvi.49.3.857-864.1984","article-title":"General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes","volume":"49","author":"Mackett","year":"1984","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nm.1935","article-title":"Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge","volume":"15","author":"Hansen","year":"2009","journal-title":"Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature10003","article-title":"Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine","volume":"473","author":"Hansen","year":"2011","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1016\/j.vaccine.2013.05.071","article-title":"Immunogenicity and safety of the vaccinia virus LC16m8delta vector expressing SIV Gag under a strong or moderate promoter in a recombinant BCG prime-recombinant vaccinia virus boost protocol","volume":"31","author":"Sato","year":"2013","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/infdis\/jiu003","article-title":"Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles","volume":"210","author":"Goepfert","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e51633","DOI":"10.1371\/journal.pone.0051633","article-title":"Elicitation of both anti HIV-1 Env humoral and cellular immunities by replicating vaccinia prime sendai virus boost regimen and boosting by CD40Lm","volume":"7","author":"Zhang","year":"2012","journal-title":"PLoS One"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/2\/4\/755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:17:03Z","timestamp":1760217423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/2\/4\/755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,17]]},"references-count":95,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,12]]}},"alternative-id":["vaccines2040755"],"URL":"https:\/\/doi.org\/10.3390\/vaccines2040755","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,17]]}}}