Poxvirus deletion mutants: virulence and immunogenicity

Kathryn M. Edwards, Thoms C. Andrews, John Van Savage, Pamela S. Palmer, Richard W. Moyer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Post-vaccinial encephalitis and disseminated vaccinia are major concerns with the use of vaccinia virus recombinants as immunization vectors in man. To identify and characterize possible attenuated poxvirus vectors, rabbitpox virus (RPV) (closely related to vaccinia) and four deletion mutants of RPV were studied for organ tropism, neurovirulence, and protection from wild-type challenge in BALB/c mice. Intraperitoneal (IP) inoculation with 107 PFU wild-type (wt) RPV or with two mutants 8 sm and 28 (containing approximately 12 kilobase deletions) showed titers of > 103 PFU/g tissue in multiple organs. In contrast, IP inoculation of 107 PFU of mutants 31 or 23 (containing approximately 30 kilobase deletions) showed markedly reduced growth in all organs. Neurovirulence of wt and mutant RPV was determined by intracerebral (IC) inoculation of mice. Wt and mutants 8 sm, and 28 RPV had LD50 < 102 PFU; in contrast, 31 and 23 had LD50 > 105 PFU. Finally, 106 PFU of mutants 31 or 23, were administered to mice by scarification, the normal route of vaccinia immunization. Both 31 and 23 grew locally in the skin and protected mice challenged IC at 21 days with 100 LD50 of wt RPV, while all unimmunized controls died. We conclude that deletion mutants 31 and 23 demonstrate markedly reduced invasiveness and neurovirulence while retaining immunogenicity. Similar deletion mutations in vaccinia may create avirulent, but effective vaccine vectors for man.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalMicrobial Pathogenesis
Volume4
Issue number5
DOIs
StatePublished - 1988

Fingerprint

Poxviridae
Vaccinia virus
Virulence
Vaccinia
Lethal Dose 50
Immunization
Tropism
Sequence Deletion
Encephalitis
Vaccines
Skin
Growth

Keywords

  • post-vaccinial encephalitis
  • poxvirus
  • rabbitpox virus
  • vaccine vectors
  • vaccinia

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Edwards, K. M., Andrews, T. C., Van Savage, J., Palmer, P. S., & Moyer, R. W. (1988). Poxvirus deletion mutants: virulence and immunogenicity. Microbial Pathogenesis, 4(5), 325-333. https://doi.org/10.1016/0882-4010(88)90060-5

Poxvirus deletion mutants : virulence and immunogenicity. / Edwards, Kathryn M.; Andrews, Thoms C.; Van Savage, John; Palmer, Pamela S.; Moyer, Richard W.

In: Microbial Pathogenesis, Vol. 4, No. 5, 1988, p. 325-333.

Research output: Contribution to journalArticle

Edwards, KM, Andrews, TC, Van Savage, J, Palmer, PS & Moyer, RW 1988, 'Poxvirus deletion mutants: virulence and immunogenicity', Microbial Pathogenesis, vol. 4, no. 5, pp. 325-333. https://doi.org/10.1016/0882-4010(88)90060-5
Edwards KM, Andrews TC, Van Savage J, Palmer PS, Moyer RW. Poxvirus deletion mutants: virulence and immunogenicity. Microbial Pathogenesis. 1988;4(5):325-333. https://doi.org/10.1016/0882-4010(88)90060-5
Edwards, Kathryn M. ; Andrews, Thoms C. ; Van Savage, John ; Palmer, Pamela S. ; Moyer, Richard W. / Poxvirus deletion mutants : virulence and immunogenicity. In: Microbial Pathogenesis. 1988 ; Vol. 4, No. 5. pp. 325-333.
@article{fabcb062bd9d4aa5805ea20c2e5cb9b0,
title = "Poxvirus deletion mutants: virulence and immunogenicity",
abstract = "Post-vaccinial encephalitis and disseminated vaccinia are major concerns with the use of vaccinia virus recombinants as immunization vectors in man. To identify and characterize possible attenuated poxvirus vectors, rabbitpox virus (RPV) (closely related to vaccinia) and four deletion mutants of RPV were studied for organ tropism, neurovirulence, and protection from wild-type challenge in BALB/c mice. Intraperitoneal (IP) inoculation with 107 PFU wild-type (wt) RPV or with two mutants 8 sm and 28 (containing approximately 12 kilobase deletions) showed titers of > 103 PFU/g tissue in multiple organs. In contrast, IP inoculation of 107 PFU of mutants 31 or 23 (containing approximately 30 kilobase deletions) showed markedly reduced growth in all organs. Neurovirulence of wt and mutant RPV was determined by intracerebral (IC) inoculation of mice. Wt and mutants 8 sm, and 28 RPV had LD50 < 102 PFU; in contrast, 31 and 23 had LD50 > 105 PFU. Finally, 106 PFU of mutants 31 or 23, were administered to mice by scarification, the normal route of vaccinia immunization. Both 31 and 23 grew locally in the skin and protected mice challenged IC at 21 days with 100 LD50 of wt RPV, while all unimmunized controls died. We conclude that deletion mutants 31 and 23 demonstrate markedly reduced invasiveness and neurovirulence while retaining immunogenicity. Similar deletion mutations in vaccinia may create avirulent, but effective vaccine vectors for man.",
keywords = "post-vaccinial encephalitis, poxvirus, rabbitpox virus, vaccine vectors, vaccinia",
author = "Edwards, {Kathryn M.} and Andrews, {Thoms C.} and {Van Savage}, John and Palmer, {Pamela S.} and Moyer, {Richard W.}",
year = "1988",
doi = "10.1016/0882-4010(88)90060-5",
language = "English (US)",
volume = "4",
pages = "325--333",
journal = "Microbial Pathogenesis",
issn = "0882-4010",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - Poxvirus deletion mutants

T2 - virulence and immunogenicity

AU - Edwards, Kathryn M.

AU - Andrews, Thoms C.

AU - Van Savage, John

AU - Palmer, Pamela S.

AU - Moyer, Richard W.

PY - 1988

Y1 - 1988

N2 - Post-vaccinial encephalitis and disseminated vaccinia are major concerns with the use of vaccinia virus recombinants as immunization vectors in man. To identify and characterize possible attenuated poxvirus vectors, rabbitpox virus (RPV) (closely related to vaccinia) and four deletion mutants of RPV were studied for organ tropism, neurovirulence, and protection from wild-type challenge in BALB/c mice. Intraperitoneal (IP) inoculation with 107 PFU wild-type (wt) RPV or with two mutants 8 sm and 28 (containing approximately 12 kilobase deletions) showed titers of > 103 PFU/g tissue in multiple organs. In contrast, IP inoculation of 107 PFU of mutants 31 or 23 (containing approximately 30 kilobase deletions) showed markedly reduced growth in all organs. Neurovirulence of wt and mutant RPV was determined by intracerebral (IC) inoculation of mice. Wt and mutants 8 sm, and 28 RPV had LD50 < 102 PFU; in contrast, 31 and 23 had LD50 > 105 PFU. Finally, 106 PFU of mutants 31 or 23, were administered to mice by scarification, the normal route of vaccinia immunization. Both 31 and 23 grew locally in the skin and protected mice challenged IC at 21 days with 100 LD50 of wt RPV, while all unimmunized controls died. We conclude that deletion mutants 31 and 23 demonstrate markedly reduced invasiveness and neurovirulence while retaining immunogenicity. Similar deletion mutations in vaccinia may create avirulent, but effective vaccine vectors for man.

AB - Post-vaccinial encephalitis and disseminated vaccinia are major concerns with the use of vaccinia virus recombinants as immunization vectors in man. To identify and characterize possible attenuated poxvirus vectors, rabbitpox virus (RPV) (closely related to vaccinia) and four deletion mutants of RPV were studied for organ tropism, neurovirulence, and protection from wild-type challenge in BALB/c mice. Intraperitoneal (IP) inoculation with 107 PFU wild-type (wt) RPV or with two mutants 8 sm and 28 (containing approximately 12 kilobase deletions) showed titers of > 103 PFU/g tissue in multiple organs. In contrast, IP inoculation of 107 PFU of mutants 31 or 23 (containing approximately 30 kilobase deletions) showed markedly reduced growth in all organs. Neurovirulence of wt and mutant RPV was determined by intracerebral (IC) inoculation of mice. Wt and mutants 8 sm, and 28 RPV had LD50 < 102 PFU; in contrast, 31 and 23 had LD50 > 105 PFU. Finally, 106 PFU of mutants 31 or 23, were administered to mice by scarification, the normal route of vaccinia immunization. Both 31 and 23 grew locally in the skin and protected mice challenged IC at 21 days with 100 LD50 of wt RPV, while all unimmunized controls died. We conclude that deletion mutants 31 and 23 demonstrate markedly reduced invasiveness and neurovirulence while retaining immunogenicity. Similar deletion mutations in vaccinia may create avirulent, but effective vaccine vectors for man.

KW - post-vaccinial encephalitis

KW - poxvirus

KW - rabbitpox virus

KW - vaccine vectors

KW - vaccinia

UR - http://www.scopus.com/inward/record.url?scp=0023735085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023735085&partnerID=8YFLogxK

U2 - 10.1016/0882-4010(88)90060-5

DO - 10.1016/0882-4010(88)90060-5

M3 - Article

C2 - 2853813

AN - SCOPUS:0023735085

VL - 4

SP - 325

EP - 333

JO - Microbial Pathogenesis

JF - Microbial Pathogenesis

SN - 0882-4010

IS - 5

ER -