Foot-and-Mouth Disease Virus Lacking the Leader Protein and Containing Two Negative DIVA Markers (FMDV LL3B3D A 24 ) Is Highly Attenuated in Pigs
Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recomb...
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Published in | Pathogens (Basel) Vol. 9; no. 2; p. 129 |
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Main Authors | , , , , , , , , , |
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Abstract | Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012,
86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3B
3D
A
encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3B
3D
A
virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3B
3D
A
is highly attenuated in pigs. |
---|---|
AbstractList | Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012,
J Virol
86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3B
PVKV
3D
YR
A
24
encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3B
PVKV
3D
YR
A
24
virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3B
PVKV
3D
YR
A
24
is highly attenuated in pigs. Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, J Virol 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3BPVKV3DYR A24 encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3BPVKV3DYR A24 virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3BPVKV3DYR A24 is highly attenuated in pigs. Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3B 3D A encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3B 3D A virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3B 3D A is highly attenuated in pigs. |
Author | Eschbaumer, Michael Stenfeldt, Carolina Krug, Peter W Dill, Veronika Arzt, Jonathan Rodriguez, Luis L Rieder, Elizabeth Carlson, Jolene C Hardham, John M Stegner, Jacob E |
AuthorAffiliation | 2 Plum Island Animal Disease Center, USDA/ARS, Orient, NY 11957, USA; jonathan.arzt@usda.gov (J.A.); carolina.stenfeldt@usda.gov (C.S.); peter.krug@nih.gov (P.W.K.); luis.rodriguez@usda.gov (L.L.R.); elizabeth.rieder@usda.gov (E.R.) 1 Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems 17493, Germany; veronika.dill@fli.de (V.D.); jolene.carlson@fli.de (J.C.C.) 4 Zoetis Inc., Kalamazoo, MI 49007, USA; john.m.hardham@zoetis.com (J.M.H.); c726087@gmail.com (J.E.S.) 3 Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66506, USA |
AuthorAffiliation_xml | – name: 4 Zoetis Inc., Kalamazoo, MI 49007, USA; john.m.hardham@zoetis.com (J.M.H.); c726087@gmail.com (J.E.S.) – name: 1 Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald - Insel Riems 17493, Germany; veronika.dill@fli.de (V.D.); jolene.carlson@fli.de (J.C.C.) – name: 3 Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66506, USA – name: 2 Plum Island Animal Disease Center, USDA/ARS, Orient, NY 11957, USA; jonathan.arzt@usda.gov (J.A.); carolina.stenfeldt@usda.gov (C.S.); peter.krug@nih.gov (P.W.K.); luis.rodriguez@usda.gov (L.L.R.); elizabeth.rieder@usda.gov (E.R.) |
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Cites_doi | 10.1177/1040638719870859 10.1016/j.molimm.2011.09.009 10.1111/j.1865-1682.2011.01236.x 10.1016/S0264-410X(98)00029-2 10.1016/j.bbrc.2010.07.044 10.1006/viro.1996.8309 10.1128/JVI.01467-07 10.1016/j.vaccine.2009.08.039 10.1016/j.rvsc.2014.01.009 10.1371/journal.ppat.1000050 10.1128/JVI.00081-17 10.1586/erv.11.4 10.1371/journal.pone.0106859 10.1128/CMR.17.2.465-493.2004 10.1016/S0168-1702(02)00261-7 10.4142/jvs.2010.11.2.133 10.1186/1297-9716-44-116 10.1006/viro.1993.1267 10.1128/JCM.03370-12 10.1016/j.jviromet.2017.04.007 10.1128/JVI.01254-12 |
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Keywords | DIVA foot-and-mouth disease virus attenuated marker virus leaderless |
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Title | Foot-and-Mouth Disease Virus Lacking the Leader Protein and Containing Two Negative DIVA Markers (FMDV LL3B3D A 24 ) Is Highly Attenuated in Pigs |
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