Lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats.
A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-gamma) as a potential vaccine strategy. We previously showed that IFN-gamma expression by pseudotyped SIVs does not alter viral single-cycle infectivity. T cells primed with dendritic cells transduced by pseudotyped SIVs expressing high levels of IFN-gamma had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-gamma. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-gamma (dSIV(LRgamma)) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-gamma (dSIV(R)). Rats vaccinated with dSIV(LRgamma) also had lower viral loads than those vaccinated with dSIV(R) when inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-gamma (dSIV(HRgamma)) did not further enhance immunity and was less protective than dSIV(LRgamma). In conclusion, the data indicated that IFN-gamma functioned as an adjuvant to augment antigen-specific immune responses in a dose- and cell type-related manner in vivo. Thus, fine-tuning of the cytokine expression appears to be essential in designing vaccine vectors expressing adjuvant genes such as the gene for IFN-gamma. Furthermore, we provide evidence of the utility of the rat model to evaluate the immunogenicities of single-cycle HIV/SIV recombinant vaccines before initiating studies with nonhuman primate models.
Peng
Yue
Y
University of California, Davis, 95616, USA.
Lin
Fan-ching
FC
Verardi
Paulo H
PH
Jones
Leslie A
LA
Yilma
Tilahun D
TD
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051381:Rats; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018116:Vesiculovirus / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000517:prevention & control
D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D007371:Interferon-gamma