Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2.
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 (greater than 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.
Flexner
C
C
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Moss
B
B
London
W T
WT
Murphy
B R
BR
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D004901:Erythrocebus patas; D005822:Genetic Vectors; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014765:Viral Vaccines / Q000276:immunology*; D014774:Virulence
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007376:Interleukin-2; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines