{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:47:23Z","timestamp":1791388043639,"version":"4.3.3"},"reference-count":82,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. By using a set of 59 nonredundant, full-genome sequences of type 2 PRRSVs, a consensus genome (designated PRRSV-CON) was generated by aligning these 59 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the synthetic PRRSV-CON strain was generated through the use of reverse genetics. PRRSV-CON replicates as efficiently as our prototype PRRSV strain FL12, both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Importantly, when inoculated into pigs, PRRSV-CON confers significantly broader levels of heterologous protection than does wild-type PRRSV. Collectively, our data demonstrate that PRRSV-CON can serve as an excellent candidate for the development of a broadly protective PRRSV vaccine.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The extraordinary genetic variation of RNA viruses poses a monumental challenge for the development of broadly protective vaccines against these viruses. To minimize the genetic dissimilarity between vaccine immunogens and contemporary circulating viruses, computational strategies have been developed for the generation of artificial immunogen sequences (so-called \u201ccentralized\u201d sequences) that have equal genetic distances to the circulating viruses. Thus far, the generation of centralized vaccine immunogens has been carried out at the level of individual viral proteins. We expand this concept to PRRSV, a highly variable RNA virus, by creating a synthetic PRRSV strain based on a centralized PRRSV genome sequence. This study provides the first example of centralizing the whole genome of an RNA virus to improve vaccine coverage. This concept may be significant for the development of vaccines against genetically variable viruses that require active viral replication in order to achieve complete immune protection.<\/jats:p>","DOI":"10.1128\/jvi.01657-15","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T02:37:56Z","timestamp":1443062276000},"page":"12070-12083","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["A Synthetic Porcine Reproductive and Respiratory Syndrome Virus Strain Confers Unprecedented Levels of Heterologous Protection"],"prefix":"10.1128","volume":"89","author":[{"given":"Hiep L. X.","family":"Vu","sequence":"first","affiliation":[{"name":"Nebraska Center for Virology, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"},{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangrui","family":"Ma","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Laegreid","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asit K.","family":"Pattnaik","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"},{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Steffen","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Doster","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A.","family":"Osorio","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"},{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska\u2014Lincoln, Lincoln, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.54846\/jshap\/754","article-title":"Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers","volume":"21","author":"Holtkamp DJ","year":"2013","unstructured":"Holtkamp DJ, Kliebenstein JB, Neumann EJ, Zimmerman J, Rotto HF, Yoder TK, Wang C, Yeske PE, Mowrer CL, Haley CA. 2013. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. J Swine Health Prod 21:72\u201384.","journal-title":"J Swine Health Prod"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063879200400201"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/01652176.1991.9694296"},{"key":"e_1_3_3_5_2","first-page":"629","article-title":"Nidovirales: a new order comprising Coronaviridae and Arteriviridae","volume":"142","author":"Cavanagh D","year":"1997","unstructured":"Cavanagh D. 1997. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 142:629\u2013633.","journal-title":"Arch Virol"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.056341-0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.04.054"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2012.06.024"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00483-08"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.04.071"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2007.02.009"},{"key":"e_1_3_3_12_2","first-page":"176","volume-title":"University of Minnesota","author":"Osorio FA","year":"1998","unstructured":"Osorio FA, Zuckermann F, Wills R, Meier W, Christian S, Galeota J, Doster A. 1998. PRRSV: comparison of commercial vaccines in their ability to induce protection against current PRRSV strains of high virulence, p 176\u2013182. In Proceedings of the 25th Allen D. Leman Swine Conference. University of Minnesota, Minneapolis, MN."},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1136\/vr.161.24.809","article-title":"Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with PRRSV","volume":"161","author":"Scortti M","year":"2007","unstructured":"Scortti M, Prieto C, Alvarez E, Simarro I, Castro JM. 2007. Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with PRRSV. Vet Rec 161:809\u2013813.","journal-title":"Vet Rec"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1746-6148-8-182"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.05.008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.70.1017"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.54846\/jshap\/421","article-title":"Genomic homology of ORF 5 gene sequence between modified live vaccine virus and porcine reproductive and respiratory syndrome virus challenge isolates is not predictive of vaccine efficacy","volume":"13","author":"Opriessnig T","year":"2005","unstructured":"Opriessnig T, Pallar\u00e9s FJ, Nilubol D. 2005. Genomic homology of ORF 5 gene sequence between modified live vaccine virus and porcine reproductive and respiratory syndrome virus challenge isolates is not predictive of vaccine efficacy. J Swine Health Prod 13:246\u2013253.","journal-title":"J Swine Health Prod"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-45-12"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00001-15"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.03.077"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-2-307"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.1.270-280.1999"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000526"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02551-09"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.4750-4763.2002"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.07.009"},{"key":"e_1_3_3_27_2","first-page":"71","article-title":"Eradication of porcine reproductive and respiratory syndrome virus by serum inoculation of naive gilts","volume":"69","author":"Fano E","year":"2005","unstructured":"Fano E, Olea L, Pijoan C. 2005. Eradication of porcine reproductive and respiratory syndrome virus by serum inoculation of naive gilts. Can J Vet Res 69:71\u201374.","journal-title":"Can J Vet Res"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00426-1"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066645"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.09.005"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.51.1.151"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070441"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.3.4.S161"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.11.5435-5451.2002"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803352105"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019744108"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806901105"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02484-05"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00383-15"},{"key":"e_1_3_3_40_2","volume-title":"Guide for the care and use of agricultural animals in research and teaching","author":"FASS Writing Committee","year":"2010","unstructured":"FASS Writing Committee. 2010. Guide for the care and use of agricultural animals in research and teaching, 3rd ed. FASS, Chicago, IL.","edition":"3"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01313785"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-0934(02)00085-X"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1612"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007050070079"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.07.020"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.31.12.3184-3189.1993"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.04.046"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.09.032"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp033"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/sysbio\/syq010"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00189-11"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.1034"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.8.3994-4004.2006"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098589503200606"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007050050256"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00513-07"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-10-48"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1593"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1119392"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00551-07"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030010"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808116105"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004420"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2237126100"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072266"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05181"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00738-06"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155761"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.2.1154-1163.2005"},{"key":"e_1_3_3_71_2","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.2460\/ajvr.1999.60.08.1022","article-title":"Evaluation of protective immunity in gilts inoculated with the NADC-8 isolate of porcine reproductive and respiratory syndrome virus (PRRSV) and challenge-exposed with an antigenically distinct PRRSV isolate","volume":"60","author":"Lager KM","year":"1999","unstructured":"Lager KM, Mengeling WL, Brockmeier SL. 1999. Evaluation of protective immunity in gilts inoculated with the NADC-8 isolate of porcine reproductive and respiratory syndrome virus (PRRSV) and challenge-exposed with an antigenically distinct PRRSV isolate. Am J Vet Res 60:1022\u20131027.","journal-title":"Am J Vet Res"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.09.013"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.22.10834-10837.2000"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.1.58-62.2003"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01789-12"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00304-06"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2004.09.005"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80959-0"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2011.11.019"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2004.09.012"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2005.07.026"},{"key":"e_1_3_3_83_2","volume-title":"The Animal Welfare Act: background and selected animal welfare legislation","author":"Cowan T","year":"2013","unstructured":"Cowan T. 2013. The Animal Welfare Act: background and selected animal welfare legislation. Congressional Research Service, Washington, DC. http:\/\/nationalaglawcenter.org\/wp-content\/uploads\/assets\/crs\/RS22493.pdf."}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01657-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01657-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T19:51:56Z","timestamp":1748634716000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01657-15"}},"subtitle":[],"editor":[{"given":"M. S.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":82,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1128\/JVI.01657-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01657-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]},"assertion":[{"value":"2015-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}