Augmentation of antigen-specific cytokine responses in the early phase of vaccination with a live-attenuated simian/human immunodeficiency chimeric virus expressing IFN-gamma.
A nef-deleted SHIV-NM-3rN (SHIV-NI) was previously shown to be nonpathogenic and to induce protective immunity. In the present study, a SHIV-NI expressing human interferon-gamma (SHIV-IFN-gamma) was constructed and the effect of co-expression of IFN-gamma on virus replication and immunopotentiation was investigated in macaques that were vaccinated with both viruses, by comparing cytokine responses during the first 4 weeks after vaccination. Peripheral blood mononuclear cells (PBMC) isolated from vaccinated macaques were stimulated with inactivated viral particles for 24 h, and the production of IL-2, IL-4, IL-6, IL-10, IL-12, TNF-alpha and IFN-gamma was determined by ELISA and flow cytometry. All of the vaccinated macaques showed increases in cytokine production. However, the production of IFN-gamma (Th1-type cytokine) was more rapidly induced by SHIV-IFN-gamma vaccination, and IFN-gamma-producing cells appeared to be still increasing at 4 weeks after vaccination, although the difference of virus replication during the time was not significant in contrast to in vitro replication in cultured PBMC. These results suggest that co-expression of IFN-gamma with SHIV can modulate the antiviral immune responses into the Th1 type response, which would probably provide more protective immunity.
Iida
T
T
Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kuwata
T
T
Ui
M
M
Suzuki
H
H
Miura
T
T
Ibuki
K
K
Takahashi
H
H
Yamamoto
T
T
Imanishi
J
J
Hayami
M
M
Kita
M
M
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D017353:Gene Deletion; D015754:Genes, nef / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
D016207:Cytokines; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma