Influence of IFNγ co-expression on the safety and antiviral efficacy of recombinant fowlpox virus HIV therapeutic vaccines following interruption of antiretroviral therapy

Sean Emery, Anthony D. Kelleher, Cassy Workman, Rebekah L. Puls, Mark Bloch, David Baker, Jonathan Anderson, Jennifer Hoy, Susanna Ip, Kellie Nalliah, Larry D. Ward, Matthew G. Law, David A. Cooper

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26 Citations (Scopus)

Abstract

Therapeutic immunization to stimulate host immune responses and control human immunodeficiency virus (HIV-1) replication is being investigated as a supplimentary treatment for the management of HIV infection. On completion of an earlier study involving three vaccinations while taking combination antiretroviral therapy (CART), twenty-five subjects with plasma viral load (pVL) <50 copies/mL received a booster vaccination with either placebo (n = 7); fowl pox vaccine (rFPV) expressing HIV-1 Gag/Pol; [partial construct - PC (n = 8)] or rFPV coexpressing HIV-1 Gag/Pol and human interferon-γ [full construct - FC (n = 10)]. One week after the booster vaccination, participants stopped ART and were monitored for safety, pVL and immunological parameters for ≤20 weeks. The time weighted mean change (SD) from baseline plasma HIV RNA was 1.80 (0.72), 1.78 (0.91) and 0.96 (0.91) log10 copies/mL for placebo, PC and FC recipients respectively (p = 0.06; mean differences between placebo and FC). Laboratory evaluations did not reveal differences in anti-HIV specific immune responses between study arms. No difference between treatment arms for host genetic factors known to affect pVL was demonstrated. In conclusion, vaccination with FC was associated with a trend toward lower rates of HIV replication following cessation of ART relative to placebo or PC. The promising antiretrovirological effect supports further study of FC in a larger trial with a broader population of patients with HIV disease.

Original languageEnglish
Pages (from-to)260-267
Number of pages8
JournalHuman Vaccines
Volume3
Issue number6
DOIs
Publication statusPublished - 1 Jan 2007

Keywords

  • HIV
  • Pox virus vector vaccine
  • Therapeutic vaccine

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