Lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats

Yue Peng, Fan Ching Lin, Paulo H. Verardi, Leslie A. Jones, Tilahun Yilma

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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-γ) as a potential vaccine strategy. We previously showed that IFN-γ 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-γ had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-γ. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-γ (dSIVLRγ) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-γ (dSIVR). Rats vaccinated with dSIVLRγ also had lower viral loads than those vaccinated with dSIVR when inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-γ (dSIVHRγ) did not further enhance immunity and was less protective than dSIVLRγ. In conclusion, the data indicated that IFN-γ 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-γ. 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.

Original languageEnglish (US)
Pages (from-to)1592-1601
Number of pages10
JournalJournal of Virology
Volume83
Issue number4
DOIs
StatePublished - Feb 2009

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
interferons
interferon-gamma
Interferons
Interferon-gamma
immune response
rats
Vaccines
animal models
dendritic cells
Dendritic Cells
adjuvants
T-lymphocytes
HIV
vaccines
Vesiculovirus
T-Lymphocytes
vector vaccines
Vaccinia virus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats. / Peng, Yue; Lin, Fan Ching; Verardi, Paulo H.; Jones, Leslie A.; Yilma, Tilahun.

In: Journal of Virology, Vol. 83, No. 4, 02.2009, p. 1592-1601.

Research output: Contribution to journalArticle

Peng, Yue ; Lin, Fan Ching ; Verardi, Paulo H. ; Jones, Leslie A. ; Yilma, Tilahun. / Lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats. In: Journal of Virology. 2009 ; Vol. 83, No. 4. pp. 1592-1601.
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