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.

Abstract

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 13 Issue 9 Pg. e0202753 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30235286 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• AIDS Vaccines
• Vaccines, Attenuated
• Vaccines, DNA
• gag Gene Products, Human Immunodeficiency Virus
• Interleukin-12

Topics

• AIDS Vaccines (administration & dosage, adverse effects)
• Adult
• Combined Modality Therapy
• Double-Blind Method
• Electroporation
• Female
• Genetic Vectors (administration & dosage, adverse effects)
• HIV-1
• Healthy Volunteers
• Humans
• Immunization, Secondary
• Injections, Intramuscular
• Interleukin-12 (genetics)
• Male
• Middle Aged
• Plasmids (genetics)
• Vaccines, Attenuated (administration & dosage, adverse effects)
• Vaccines, DNA (administration & dosage, adverse effects)
• Vesicular stomatitis Indiana virus (genetics)
• Young Adult
• gag Gene Products, Human Immunodeficiency Virus