Porcine circovirus 2 85708 PCV2 binds to heparin sulfate and chondroitin sulfate, which are glycosaminoglycans (GAGs), as a 1st step of attachment. However, as PCV2 is found in cells that lack GAGs, it is thought that another coreceptor is also used for viral entry. The hallmark lesion of PCV2 infection is lymphoid depletion with histiocytic replacement. In affected lymph organs, dendritic cells, and macrophages that replace the lymphocytes contain large amounts of PCV2 virus. There is no viral degradation in these cells, and because dendritic cells are highly mobile, it is thought that dendritic mobility may be a method of viral dissemination in tissues. It is still unknown how PCV2 causes a reduction in lymphocytes. Hypotheses include induced apoptosis, decreased lymphocyte production in the bone marrow, or reduced lymphocyte proliferation in secondary lymphoid tissue (Gillespie et al., 2009). Postweaning multisystemic wasting syndrome Because most breeding age sows are seropositive for PCV2, most piglets are born with maternal antibodies against PCV2. In weaned piglets, the mean half life of antibodies is 19 days. Antibody levels will wane at 4–6 weeks in pigs with initially low levels of antibody, at 6–10 weeks with moderate antibody levels, and by 8.5–13.5 weeks in pigs with high antibody levels. Piglets do not typically demonstrate clinical signs of disease before 4 weeks of age, suggesting that maternally derived antibodies are protective. Experimental studies found that maternal antibody protection is dependent on the level of maternal antibodies present. High levels of maternal antibodies are more protective than low levels, but do not completely prevent infection, whereas low levels of antibodies did not provide any protection against infection (Gillespie et al., 2009). Porcine Circovirus (PCV) is a single stranded DNA virus (class II), that is non-enveloped with an un-segmented circular genome. The viral capsid is icosahedral and approximately 17 nm in diameter. PCV is a member of the virus family Circoviridae. PCV are the smallest viruses replicating autonomously in eukaryotic cells. They replicate in the nucleus of infected cells, utilising the host polymerase for genome amplification. There are 2 strains: Type 1 PCV and Type 2 PCV. It is still unclear whether type 2 PCV (first isolated in 1997) actually causes PMWS, as infection with the virus alone causes no clinical signs, it appears to work synergistically with parvovirus, perhaps with parvovirus activating a latent form of circovirus or weakening the immune system enough for PCV to take hold. PCV1 and PCV2 show a high degree of sequence identity and a similar genomic organisation; nevertheless, the basis of the distinct pathogenicity has not yet been unravelled (Wiki: Porcine circovirus). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 BV-GD-ORF2 VO_0004754 Recombinant vector vaccine Research Intramuscular injection (i.m.) B aculovirus was used to develop a novel candidate vaccine for a preventive or therapeutic strategy to control PCV2 infections (Ye et al., 2013). Intramuscular injection (i.m.) BALB/c mice were immunized intramuscularly with this baculovirus (Ye et al., 2013). VO_0003057 The vaccination of mice with recombinant baculovirus BV-GD-ORF2 successfully induced robust Cap-protein-specific humoral and cellular immune responses (Ye et al., 2013). PCV2 DNA Vaccine encoding ORF2 Protein VO_0011481 DNA vaccine Research pCI-neo [Ref1247:Shen et al., 2008] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction BALB/c The mice in the vaccine groups were injected intramuscularly in the quadriceps with 100 µg pORF2 plasmid prepared in 100 µl PBS as follows. The mice in the pORF2 group received vaccination with pORF2 plasmid, three times every 2 weeks, whilst those in the pORF2/Cap or Cap/pORF2 group were primed with pORF2 plasmid (or Cap protein) and boosted with doses of Cap protein (or pORF2 plasmid) twice every 2 weeks (Shen et al., 2008). Following virus challenge, real-time PCR and histopathological analysis confirmed that only low viral DNA loads and mild microscopic lesions appeared in pORF2-immunized mice (Shen et al., 2008). At 16 weeks p.i., the mice were challenged intraperitoneally with 0.2 ml PCV2 inoculum (105.75 TCID50 1/ml) (Shen et al., 2008). Serum IgG1 was significantly higher in mice immunized with PCV2 DNA vaccine encoding ORF2 protein than control mice, vaccinated with the pCI-neo vector and crude lysate of E. coli strain BL21 transformed with pGEX-4T-1 were used as substitutes for pORF2 plasmid and Cap protein, respectively. The up regulation began 4 weeks after immunization (Shen et al., 2008). Serum IgG2a was significantly higher in mice immunized with PCV2 DNA vaccine encoding ORF2 protein than control mice, vaccinated with the pCI-neo vector and crude lysate of E. coli strain BL21 transformed with pGEX-4T-1 were used as substitutes for pORF2 plasmid and Cap protein, respectively. The up regulation began 4 weeks after immunization (Shen et al., 2008). Porcilis-PCV2 Porcilis-PCV2 Intervet VO_0000201 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Inactivated baculovirus expressed PCV2 ORF2 protein; adjuvanted (Wang et al., 2007). Intramuscular injection (i.m.) Porcine Circovirus Type 1 - Type 2 Chimera, Killed Virus Vaccine (USDA: 19K5.R1) Wyeth VO_0002195 Inactivated or "killed" vaccine Licensed USA Porcine Circovirus Type 2, Killed Baculovirus Vector Vaccine (USDA: 19K5.R0) Boehringer Ingelheim Vetmedica, Inc., Intervet Inc. VO_0001825 Inactivated or "killed" vaccine Licensed USA Porcine Circovirus Type 2, Killed Baculovirus Vector Vaccine- Mycoplasma Hyopneumoniae Bacterin (USDA: 49K5.R1) Boehringer Ingelheim Vetmedica, Inc. VO_0002316 Inactivated or "killed" vaccine Licensed USA Porcine Circovirus Type 2, Killed Virus Vaccine (USDA: 19K5.20) Merial, Inc. VO_0001798 Inactivated or "killed" vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome-Circovirus Reproductive & Respiratory Form, Type 2, Modifed Live Virus,Killed Baculovirus Vector Vaccine-Mycoplasma Hyopneumoniae Bacterin (USDA: 49K9.R0) Boehringer Ingelheim Vetmedica, Inc. VO_0002317 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA PrV-PCV2-ORF2 VO_0004699 Recombinant vector vaccine Research Intramuscular injection (i.m.) PCV2 ORF2 gene was inserted into vector pG to produce the recombinant PRV vector pGO (Chao et al., 2014). Intramuscular injection (i.m.) Recombinant vector construction PCV2 ORF2 gene was inserted into vector pG to produce the recombinant PRV vector pGO; the genome of PRV attenuated vaccine and the transfer plasmid pGO were transfected by using Lipofectamine 2000 Reagent into swine testis cells for homologous recombination to obtain the recombinant PRV (Chao et al., 2014). Six week odl mice were immunized two intramuscular immunizations 4 weeks apart (Chao et al., 2014). VO_0003057 Challenge experiments show that the recombinant virus and PCV2 inactivated vaccine could both protect the mice against PCV2 challenge, suggesting that the recombinant virus can be an excellent potential vaccine (Chao et al., 2014). Mice were then challenged with the virulent PCV2 NY strain at 8 weeks after the first immunization (Chao et al., 2014). rSPV-PCV2-cap recombinant swinepox virus expressing PCV2 capsid protein VO_0004619 Recombinant vector vaccine Research [Ref3090:Lin et al., 2012] Intramuscular injection (i.m.) Recombinant swinepox virus expressing capsid protein (rSPV-cap) (Lin et al., 2012). Intramuscular injection (i.m.) PCV2 capsid Pigs were immunized with rSPV-cap, wild type SPV (wtSPV; negative control), or PBS (challenge control) (Lin et al., 2012). VO_0003057 After inoculation with PCV2, pigs in the rSPV-cap immunized group showed significantly higher average daily weight gain (ADG) and shorter fever duration compared with the wtSPV treated group. The results suggested that the recombinant rSPV-cap provided pigs with significant protection from PCV2-associated disease (Lin et al., 2012). Vaccinated pigs were challenged with PCV2 (Lin et al., 2012). Suvaxyn PCV2 Suvaxyn PCV2 Fort Dodge VO_0000203 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Inactivated PCV1-2 chimera; adjuvanted (Ferrari et al., 2000) Intramuscular injection (i.m.) Ighg1 Mus musculus 16017 AC160982 Vaximmutor Ighv1-9 Mus musculus 668478 AC073561 10090 12 114583568 114583861 immunoglobulin heavy variable V1-9 Also known as Igg2a; Gm16697 >gi|372099098:114583568-114583861 Mus musculus strain C57BL/6J chromosome 12, GRCm38 C57BL/6J GTCTTGCACAGTAATAGATGGCAGAGTCCTCAGTTGTCAGGCTGCTGAGTTGCATGTAGGCTGTGTTGGA GGATGTATCTGCAGTGAATGTGGCCTTGCCCTTGAACTTCTCATTGTAGTTAGTACTACCACTTCCAGGT AAAATCTCTCCAATCCACTCAAGGCCATGTCCAGGCCTCTGCTTTACCCACTCTATCCAGTAGCCAGTGA ATGTGTAGCCAGTAGCCTTGCAGGAAAGCTTCACTGAGGCCCCAGGCTTCATCAGCTCAGCTCCAGACTG CTGCAGCTGAACCT Vaximmutor ORF2 Porcine circovirus type 2 VO_0011243 78217439 CDD:280582 85708 ? ORF2 11.34 26948.82 278 Circovirus capsid protein; pfam02443 >ABB36795.1 ORF2 [Porcine circovirus 2] MAYPRRRYRRRRHRPRSHLGQILRRRLWLLHPRHRYRWRRKNGIFNTRLSRTFGYTIKRTTVKTPSWAVD MMRFNINDFLPPGGGSNPRSVPFEYYRIRKVKVEFWPCSPITQGDRGVGSSAVILDDNFVTKATALTYDP YVNYSSRHTITQPFSYHSRYFTPKPVLDSTIDYFQPNNKRNQLWLRLQTAGNVDHVGLGTAFENSIYDQE YNIRVTMYVQFREFNLKDPPLKP Protective antigen An open reading frame 2 plasmid (pORF2) and the capsid protein (Cap) of PCV2 were used as DNA and subunit vaccines, respectively. In FCM analysis, although pORF2 and Cap alone showed comparable efficacy in eliciting lymphoproliferative responses and Cap-specific CD4(+) T cells, pORF2 was superior to the Cap protein in triggering CD8(+) T cells. Following virus challenge, real-time PCR and histopathological analysis confirmed that only low viral DNA loads and mild microscopic lesions appeared in pORF2-immunized mice [Ref1247:Shen et al., 2008]. Chao et al., 2014 journal Chao A, Fu P, Guo X, Gao X, Cui B, Chen H 2014 54 2 211-217 Wei sheng wu xue bao = Acta microbiologica Sinica Ding et al., 2017 journal Ding P, Zhang T, Li Y, Teng M, Sun Y, Liu X, Chai S, Zhou E, Jin Q, Zhang G 2017 12 5239-5254 International journal of nanomedicine Ferrari et al., 2000 journal Ferrari M, Brack A, Romanelli MG, Mettenleiter TC, Corradi A, Dal Mas N, Losio MN, Silini R, Pinoni C, Pratelli A 2000 47 10 753-762 Journal of veterinary medicine. B, Infectious diseases and veterinary public health Gillespie et al., 2009 journal Gillespie J, Opriessnig T, Meng XJ, Pelzer K, Buechner-Maxwell V 2009 23 6 1151-1163 Journal of veterinary internal medicine / American College of Veterinary Internal Medicine Lin et al., 2012 journal Lin HX, Ma Z, Fan HJ, Lu CP 2012 30 44 6307-6313 Vaccine Shen et al., 2008 journal Shen HG, Zhou JY, Huang ZY, Guo JQ, Xing G, He JL, Yan Y, Gong LY 2008 89 Pt 8 1857-1865 The Journal of general virology Wang et al., 2007 journal Wang X, Jiang P, Li Y, Jiang W, Dong X 2007 121 3-4 215-224 Veterinary microbiology Wiki: Porcine circovirus website http://en.wikipedia.org/wiki/Porcine_circovirus Xu et al., 2013 journal Xu J, Yang D, Huang D, Xu J, Liu S, Lin H, Zhu H, Liu B, Lu C 2013 158 3 629-637 Archives of virology Ye et al., 2013 journal Ye Y, Cheng X, Zhang J, Tong T, Lin W, Liao M, Fan H 2013 10 316 Virology journal