Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2

Charles Williams Flexner, Bernard Moss, William T. London, Brian R. Murphy

Research output: Contribution to journalArticle

Abstract

Vector-directed lymphokine expression represents a novel approach to the attenuation of live recombinant viruses which might be used as vaccines. Expression of interleukin-2 (IL-2) by recombinant vaccinia virus has been shown to significantly attenuate virus virulence in rodent species without diminishing immunogenicity. Skin lesion formation and immunogenicity of vaccinia/IL-2 recombinants in three species of primates was examined. IL-2 expression was associated with a 15-fold reduction in the area of induration after intradermal inoculation of recombinant viruses in patas monkeys. Wild type and a control vaccinia recombinant produced large (> 5000 mm2) skin ulcers in this species, but the IL-2 expressing recombinant produced no ulceration. Production of antibodies to vaccinia virus and to influenza A virus haemagglutinin expressed by recombinant vectors was examined in rhesus and squirrel monkeys. IL-2 expression accelerated the resolution of skin lesions in rhesus but not squirrel monkeys. Despite this, antibody production was equivalent in the presence or absence of IL-2. IL-2 expression can greatly reduce the skin lesions formed by live recombinant vaccinia vectors in primates, indicating significant attenuation, without reducing the immunogenicity of the vaccine.

Original languageEnglish (US)
Pages (from-to)17-21
Number of pages5
JournalVaccine
Volume8
Issue number1
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

Vaccinia virus
interleukin-2
Primates
Interleukin-2
immune response
Vaccinia
Vaccinium
skin lesions
Saimiri
antibody formation
Viruses
Eubenangee virus
Skin
Antibody Formation
Erythrocebus patas
vaccines
Skin Ulcer
lymphokines
viruses
Lymphokines

Keywords

  • interleukin-2
  • Vaccinia virus
  • virus attenuation

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2. / Flexner, Charles Williams; Moss, Bernard; London, William T.; Murphy, Brian R.

In: Vaccine, Vol. 8, No. 1, 1990, p. 17-21.

Research output: Contribution to journalArticle

Flexner, Charles Williams ; Moss, Bernard ; London, William T. ; Murphy, Brian R. / Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2. In: Vaccine. 1990 ; Vol. 8, No. 1. pp. 17-21.
@article{547ebcca7d664f52ab9e69cf52a1b60d,
title = "Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2",
abstract = "Vector-directed lymphokine expression represents a novel approach to the attenuation of live recombinant viruses which might be used as vaccines. Expression of interleukin-2 (IL-2) by recombinant vaccinia virus has been shown to significantly attenuate virus virulence in rodent species without diminishing immunogenicity. Skin lesion formation and immunogenicity of vaccinia/IL-2 recombinants in three species of primates was examined. IL-2 expression was associated with a 15-fold reduction in the area of induration after intradermal inoculation of recombinant viruses in patas monkeys. Wild type and a control vaccinia recombinant produced large (> 5000 mm2) skin ulcers in this species, but the IL-2 expressing recombinant produced no ulceration. Production of antibodies to vaccinia virus and to influenza A virus haemagglutinin expressed by recombinant vectors was examined in rhesus and squirrel monkeys. IL-2 expression accelerated the resolution of skin lesions in rhesus but not squirrel monkeys. Despite this, antibody production was equivalent in the presence or absence of IL-2. IL-2 expression can greatly reduce the skin lesions formed by live recombinant vaccinia vectors in primates, indicating significant attenuation, without reducing the immunogenicity of the vaccine.",
keywords = "interleukin-2, Vaccinia virus, virus attenuation",
author = "Flexner, {Charles Williams} and Bernard Moss and London, {William T.} and Murphy, {Brian R.}",
year = "1990",
doi = "10.1016/0264-410X(90)90171-H",
language = "English (US)",
volume = "8",
pages = "17--21",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2

AU - Flexner, Charles Williams

AU - Moss, Bernard

AU - London, William T.

AU - Murphy, Brian R.

PY - 1990

Y1 - 1990

N2 - Vector-directed lymphokine expression represents a novel approach to the attenuation of live recombinant viruses which might be used as vaccines. Expression of interleukin-2 (IL-2) by recombinant vaccinia virus has been shown to significantly attenuate virus virulence in rodent species without diminishing immunogenicity. Skin lesion formation and immunogenicity of vaccinia/IL-2 recombinants in three species of primates was examined. IL-2 expression was associated with a 15-fold reduction in the area of induration after intradermal inoculation of recombinant viruses in patas monkeys. Wild type and a control vaccinia recombinant produced large (> 5000 mm2) skin ulcers in this species, but the IL-2 expressing recombinant produced no ulceration. Production of antibodies to vaccinia virus and to influenza A virus haemagglutinin expressed by recombinant vectors was examined in rhesus and squirrel monkeys. IL-2 expression accelerated the resolution of skin lesions in rhesus but not squirrel monkeys. Despite this, antibody production was equivalent in the presence or absence of IL-2. IL-2 expression can greatly reduce the skin lesions formed by live recombinant vaccinia vectors in primates, indicating significant attenuation, without reducing the immunogenicity of the vaccine.

AB - Vector-directed lymphokine expression represents a novel approach to the attenuation of live recombinant viruses which might be used as vaccines. Expression of interleukin-2 (IL-2) by recombinant vaccinia virus has been shown to significantly attenuate virus virulence in rodent species without diminishing immunogenicity. Skin lesion formation and immunogenicity of vaccinia/IL-2 recombinants in three species of primates was examined. IL-2 expression was associated with a 15-fold reduction in the area of induration after intradermal inoculation of recombinant viruses in patas monkeys. Wild type and a control vaccinia recombinant produced large (> 5000 mm2) skin ulcers in this species, but the IL-2 expressing recombinant produced no ulceration. Production of antibodies to vaccinia virus and to influenza A virus haemagglutinin expressed by recombinant vectors was examined in rhesus and squirrel monkeys. IL-2 expression accelerated the resolution of skin lesions in rhesus but not squirrel monkeys. Despite this, antibody production was equivalent in the presence or absence of IL-2. IL-2 expression can greatly reduce the skin lesions formed by live recombinant vaccinia vectors in primates, indicating significant attenuation, without reducing the immunogenicity of the vaccine.

KW - interleukin-2

KW - Vaccinia virus

KW - virus attenuation

UR - http://www.scopus.com/inward/record.url?scp=0025364053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025364053&partnerID=8YFLogxK

U2 - 10.1016/0264-410X(90)90171-H

DO - 10.1016/0264-410X(90)90171-H

M3 - Article

C2 - 2316280

AN - SCOPUS:0025364053

VL - 8

SP - 17

EP - 21

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 1

ER -