Lars Jørgen Østergaard

Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs

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  • G Tapia, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, Switzerland.
  • ,
  • J F Højen
  • ,
  • M Ökvist, Bionor Pharma AS, P.O.Box 1477 Vika, NO-0116 Oslo, Norway.
  • ,
  • R Olesen
  • S Leth
  • S K Nissen
  • D J VanBelzen, University of, Philadelphia, Pennsylvania 19104, USA.
  • ,
  • U O'Doherty, University of, Philadelphia, Pennsylvania 19104, USA.
  • ,
  • A Mørk, Bionor Pharma AS, P.O.Box 1477 Vika, NO-0116 Oslo, Norway.
  • ,
  • K Krogsgaard, Bionor Pharma AS, P.O.Box 1477 Vika, NO-0116 Oslo, Norway.
  • ,
  • O S Søgaard
  • ,
  • L Østergaard
  • M Tolstrup
  • G Pantaleo, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, Switzerland.
  • ,
  • M A Sommerfelt, Bionor Pharma AS, P.O.Box 1477 Vika, NO-0116 Oslo, Norway. Electronic address: ms@bionorpharma.com.

OBJECTIVES: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir.

METHODS: This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm(3) on cART. Six Vacc-4x (1.2 mg) intradermal immunizations using rhuGM-CSF (60 μg) as adjuvant were followed by 3 weekly intravenous infusions of romidepsin (5 mg/m(2)). Immune responses were determined by IFN-γ ELISpot, T-cell proliferation to p24 15-mer peptides covering the Vacc-4x region, intracellular cytokine staining (ICS) to the entire HIV(Gag) and viral inhibition.

RESULTS: The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%) post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006; q = 0.183), post-latency reversal (p = 0.005; q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015; q = 0.254). Participants (40%) were defined as proliferation 'Responders' having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIV(Gag) by ICS. There was a trend towards increased viral inhibition from baseline to post-vaccination (p = 0.08).

CONCLUSIONS: In this 'shock and kill' approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.

Original languageEnglish
JournalThe Journal of infection
ISSN0163-4453
DOIs
Publication statusPublished - Dec 2017

    Research areas

  • Journal Article

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