PMID- 26401031 OWN - NLM STAT- MEDLINE DCOM- 20160301 LR - 20181113 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 89 IP - 23 DP - 2015 Dec TI - A Synthetic Porcine Reproductive and Respiratory Syndrome Virus Strain Confers Unprecedented Levels of Heterologous Protection. PG - 12070-83 LID - 10.1128/JVI.01657-15 [doi] AB - 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 in vitro and in vivo. 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. IMPORTANCE: 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 "centralized" 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. CI - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved. FAU - Vu, Hiep L X AU - Vu HL AD - Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA hiepvu@unl.edu fosorio@unl.edu. FAU - Ma, Fangrui AU - Ma F AD - Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. FAU - Laegreid, William W AU - Laegreid WW AD - Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming, USA. FAU - Pattnaik, Asit K AU - Pattnaik AK AD - Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. FAU - Steffen, David AU - Steffen D AD - School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. FAU - Doster, Alan R AU - Doster AR AD - School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. FAU - Osorio, Fernando A AU - Osorio FA AD - Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA hiepvu@unl.edu fosorio@unl.edu. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150923 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Vaccines, Synthetic) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Base Sequence MH - Fluorescent Antibody Technique, Indirect MH - *Genetic Variation MH - Immunity, Heterologous/*immunology MH - Molecular Sequence Data MH - Neutralization Tests MH - Porcine Reproductive and Respiratory Syndrome/*prevention & control MH - Porcine respiratory and reproductive syndrome virus/*genetics/*immunology MH - Sequence Alignment MH - Sequence Analysis, DNA MH - Swine MH - Vaccines, Synthetic/virology MH - Viral Plaque Assay MH - Viral Vaccines/*genetics/immunology PMC - PMC4645332 EDAT- 2015/09/25 06:00 MHDA- 2016/03/02 06:00 PMCR- 2016/06/01 CRDT- 2015/09/25 06:00 PHST- 2015/06/26 00:00 [received] PHST- 2015/09/14 00:00 [accepted] PHST- 2015/09/25 06:00 [entrez] PHST- 2015/09/25 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] PHST- 2016/06/01 00:00 [pmc-release] AID - JVI.01657-15 [pii] AID - 01657-15 [pii] AID - 10.1128/JVI.01657-15 [doi] PST - ppublish SO - J Virol. 2015 Dec;89(23):12070-83. doi: 10.1128/JVI.01657-15. Epub 2015 Sep 23.