PLoS ONE (Jan 2018)

Safety and tolerability of HIV-1 multiantigen pDNA vaccine given with IL-12 plasmid DNA via electroporation, boosted with a recombinant vesicular stomatitis virus HIV Gag vaccine in healthy volunteers in a randomized, controlled clinical trial.

  • Marnie L Elizaga,
  • Shuying S Li,
  • Nidhi K Kochar,
  • Gregory J Wilson,
  • Mary A Allen,
  • Hong Van N Tieu,
  • Ian Frank,
  • Magdalena E Sobieszczyk,
  • Kristen W Cohen,
  • Brittany Sanchez,
  • Theresa E Latham,
  • David K Clarke,
  • Michael A Egan,
  • John H Eldridge,
  • Drew Hannaman,
  • Rong Xu,
  • Ayuko Ota-Setlik,
  • M Juliana McElrath,
  • Christine Mhorag Hay,
  • NIAID HIV Vaccine Trials Network (HVTN) 087 Study Team

DOI
https://doi.org/10.1371/journal.pone.0202753
Journal volume & issue
Vol. 13, no. 9
p. e0202753

Abstract

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BACKGROUND:The addition of plasmid cytokine adjuvants, electroporation, and live attenuated viral vectors may further optimize immune responses to DNA vaccines in heterologous prime-boost combinations. The objective of this study was to test the safety and tolerability of a novel prime-boost vaccine regimen incorporating these strategies with different doses of IL-12 plasmid DNA adjuvant. METHODS:In a phase 1 study, 88 participants received an HIV-1 multiantigen (gag/pol, env, nef/tat/vif) DNA vaccine (HIV-MAG, 3000 μg) co-administered with IL-12 plasmid DNA adjuvant at 0, 250, 1000, or 1500 μg (N = 22/group) given intramuscularly with electroporation (Ichor TriGrid™ Delivery System device) at 0, 1 and 3 months; followed by attenuated recombinant vesicular stomatitis virus, serotype Indiana, expressing HIV-1 Gag (VSV-Gag), 3.4 ⊆ 107 plaque-forming units (PFU), at 6 months; 12 others received placebo. Injections were in both deltoids at each timepoint. Participants were monitored for safety and tolerability for 15 months. RESULTS:The dose of IL-12 pDNA did not increase pain scores, reactogenicity, or adverse events with the co-administered DNA vaccine, or following the VSV-Gag boost. Injection site pain and reactogenicity were common with intramuscular injections with electroporation, but acceptable to most participants. VSV-Gag vaccine often caused systemic reactogenicity symptoms, including a viral syndrome (in 41%) of fever, chills, malaise/fatigue, myalgia, and headache; and decreased lymphocyte counts 1 day after vaccination. CONCLUSIONS:HIV-MAG DNA vaccine given by intramuscular injection with electroporation was safe at all doses of IL-12 pDNA. The VSV-Gag vaccine at this dose was associated with fever and viral symptoms in some participants, but the vaccine regimens were safe and generally well-tolerated. TRIAL REGISTRATION:Clinical Trials.gov NCT01578889.