Journal Article

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

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

2018

Overview

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. 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. 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. 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. Clinical Trials.gov NCT01578889.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / AIDS vaccines / AIDS Vaccines - administration & dosage / AIDS Vaccines - adverse effects / Analysis / Biology and Life Sciences / Clinical trials / Combined Modality Therapy / Double-Blind Method / Electroporation / Female / gag Gene Products, Human Immunodeficiency Virus / Genetic Vectors - administration & dosage / Genetic Vectors - adverse effects / Healthy Volunteers / HIV-1 / Humans / Immune response / Immunization, Secondary / Injections, Intramuscular / Interleukin-12 - genetics / Male / Medicine and Health Sciences / Middle Aged / Plasmids - genetics / Research and Analysis Methods / Safety and security measures / Vaccines, Attenuated - administration & dosage / Vaccines, Attenuated - adverse effects / Vaccines, DNA - administration & dosage / Vaccines, DNA - adverse effects / Vesicular stomatitis Indiana virus - genetics / Young Adult