Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions

Mathew M. Adams; Barbara H. van Leeuwen; Peter J. Kerr

doi:10.1016/j.vaccine.2008.08.036

Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions

Mathew M. Adams, Barbara H. van Leeuwen, Peter J. Kerr^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Three deletion mutant viruses were constructed as potential vaccines against myxomatosis using the naturally attenuated Uriarra strain of myxoma virus. The viruses had the M007 (encodes a secreted γ-interferon receptor homologue), M010 (encodes an epidermal growth factor homologue) and M011 (encodes an inhibitor of apoptosis in T lymphocytes) genes insertionally inactivated as either ΔM007, ΔM010/M011 or ΔM007/M010/M011. All three viruses induced high serum antibody titres. Rabbits immunized with these deletion mutants were protected from lethal challenge. However, immunization of adult rabbits with ΔM007 or ΔM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (ΔM007/M010/M011) termed Ur-TKO was very well tolerated by adult and juvenile rabbits. The low pathogenicity of Ur-TKO was confirmed by pathogenesis studies in domestic and wild rabbits. Crown

Original language	English
Pages (from-to)	5843-5854
Number of pages	12
Journal	Vaccine
Volume	26
Issue number	46
DOIs	https://doi.org/10.1016/j.vaccine.2008.08.036
Publication status	Published - 29 Oct 2008

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10.1016/j.vaccine.2008.08.036

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title = "Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions",

abstract = "Three deletion mutant viruses were constructed as potential vaccines against myxomatosis using the naturally attenuated Uriarra strain of myxoma virus. The viruses had the M007 (encodes a secreted γ-interferon receptor homologue), M010 (encodes an epidermal growth factor homologue) and M011 (encodes an inhibitor of apoptosis in T lymphocytes) genes insertionally inactivated as either ΔM007, ΔM010/M011 or ΔM007/M010/M011. All three viruses induced high serum antibody titres. Rabbits immunized with these deletion mutants were protected from lethal challenge. However, immunization of adult rabbits with ΔM007 or ΔM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (ΔM007/M010/M011) termed Ur-TKO was very well tolerated by adult and juvenile rabbits. The low pathogenicity of Ur-TKO was confirmed by pathogenesis studies in domestic and wild rabbits. Crown",

keywords = "Myxoma virus, Myxomatosis, Poxvirus, Vaccine",

author = "Adams, {Mathew M.} and {van Leeuwen}, {Barbara H.} and Kerr, {Peter J.}",

year = "2008",

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day = "29",

doi = "10.1016/j.vaccine.2008.08.036",

language = "English",

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journal = "Vaccine",

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T1 - Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions

AU - Adams, Mathew M.

AU - van Leeuwen, Barbara H.

AU - Kerr, Peter J.

PY - 2008/10/29

Y1 - 2008/10/29

N2 - Three deletion mutant viruses were constructed as potential vaccines against myxomatosis using the naturally attenuated Uriarra strain of myxoma virus. The viruses had the M007 (encodes a secreted γ-interferon receptor homologue), M010 (encodes an epidermal growth factor homologue) and M011 (encodes an inhibitor of apoptosis in T lymphocytes) genes insertionally inactivated as either ΔM007, ΔM010/M011 or ΔM007/M010/M011. All three viruses induced high serum antibody titres. Rabbits immunized with these deletion mutants were protected from lethal challenge. However, immunization of adult rabbits with ΔM007 or ΔM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (ΔM007/M010/M011) termed Ur-TKO was very well tolerated by adult and juvenile rabbits. The low pathogenicity of Ur-TKO was confirmed by pathogenesis studies in domestic and wild rabbits. Crown

AB - Three deletion mutant viruses were constructed as potential vaccines against myxomatosis using the naturally attenuated Uriarra strain of myxoma virus. The viruses had the M007 (encodes a secreted γ-interferon receptor homologue), M010 (encodes an epidermal growth factor homologue) and M011 (encodes an inhibitor of apoptosis in T lymphocytes) genes insertionally inactivated as either ΔM007, ΔM010/M011 or ΔM007/M010/M011. All three viruses induced high serum antibody titres. Rabbits immunized with these deletion mutants were protected from lethal challenge. However, immunization of adult rabbits with ΔM007 or ΔM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (ΔM007/M010/M011) termed Ur-TKO was very well tolerated by adult and juvenile rabbits. The low pathogenicity of Ur-TKO was confirmed by pathogenesis studies in domestic and wild rabbits. Crown

KW - Myxoma virus

KW - Myxomatosis

KW - Poxvirus

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=53449096677&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2008.08.036

DO - 10.1016/j.vaccine.2008.08.036

M3 - Article

SN - 0264-410X

VL - 26

SP - 5843

EP - 5854

JO - Vaccine

JF - Vaccine

IS - 46

ER -

Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions

Abstract

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