Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
PLoS One. 2018 Sep 20;13(9):e0202753. doi: 10.1371/journal.pone.0202753. eCollection 2018.
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.
在异源初免-加强免疫组合中添加质粒细胞因子佐剂、电穿孔和减毒活病毒载体可能进一步优化 DNA 疫苗的免疫反应。本研究的目的是测试包含这些策略的新型初免-加强疫苗方案的安全性和耐受性，该方案使用不同剂量的白细胞介素 12（IL-12）质粒 DNA 佐剂。
在一项 1 期研究中，88 名参与者接受了一种 HIV-1 多抗原（gag/pol、env、 nef/tat/vif）DNA 疫苗（HIV-MAG，3000μg）与 IL-12 质粒 DNA 佐剂（0、250、1000 或 1500μg，每组 22 人）联合给药，肌肉内注射并用电穿孔（Ichor TriGrid™ Delivery System 装置），在 0、1 和 3 个月时进行；然后在 6 个月时给予减毒重组水疱性口炎病毒，印第安纳血清型，表达 HIV-1 Gag（VSV-Gag），3.4 ⊆ 107 噬菌斑形成单位（PFU）；其余 12 人接受安慰剂。每次注射均在两个三角肌。参与者在 15 个月内监测安全性和耐受性。
IL-12 pDNA 的剂量并未增加与共给药 DNA 疫苗或 VSV-Gag 加强疫苗相关的疼痛评分、不良反应或不良事件，也未增加注射部位疼痛和不良反应。电穿孔肌肉内注射常见注射部位疼痛和不良反应，但大多数参与者均可接受。VSV-Gag 疫苗常引起全身不良反应症状，包括发热、寒战、不适/疲劳、肌痛和头痛的病毒综合征（41%）；以及接种后 1 天淋巴细胞计数下降。
在所有剂量的 IL-12 pDNA 下，通过肌肉内注射并用电穿孔给予 HIV-MAG DNA 疫苗是安全的。该剂量的 VSV-Gag 疫苗与一些参与者的发热和病毒症状相关，但疫苗方案是安全的，通常耐受性良好。
ClinicalTrials.gov NCT01578889。
