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.
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.
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DOI：
10.1371/journal.pone.0202753
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
NIAID HIV Vaccine Trials Network (HVTN) 087 Study Team
中科院分区：
文献类型：
--
作者：
Elizaga ML;Li SS;Kochar NK;Wilson GJ;Allen MA;Tieu HVN;Frank I;Sobieszczyk ME;Cohen KW;Sanchez B;Latham TE;Clarke DK;Egan MA;Eldridge JH;Hannaman D;Xu R;Ota-Setlik A;McElrath MJ;Hay CM;NIAID HIV Vaccine Trials Network (HVTN) 087 Study Team
质粒细胞因子佐剂、电穿孔和活减毒病毒载体的添加可以进一步优化对异源初免-加强组合中的DNA疫苗的免疫应答。本研究的目的是测试将这些策略与不同剂量的IL-12质粒DNA佐剂结合的新型初免-加强疫苗方案的安全性和耐受性。在一项1期研究中，88名参与者接受了HIV-1多抗原（gag/pol，env，nef/达特/vif）DNA疫苗（HIV-MAG，3000 μg）与0、250、1000或1500 μg IL-12质粒DNA佐剂共同给药（N = 22/组）肌内给药伴电穿孔（Ichor TriGrid™输送系统器械）在0、1和3个月时;随后是减毒重组水泡性口炎病毒，印第安纳州血清型，表达HIV-1 Gag（VSV-Gag），6个月时为3.4 × 107空斑形成单位（PFU）;另外12人服用安慰剂。在每个时间点在两个三角肌中注射。参与者被监测15个月的安全性和耐受性。IL-12 pDNA的剂量不增加疼痛评分、反应原性或与共同施用的DNA疫苗一起或在VSV-Gag加强后的不良事件。注射部位疼痛和反应原性是常见的肌肉注射与电穿孔，但大多数参与者可以接受。VSV-Gag疫苗通常引起全身反应原性症状，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天淋巴细胞计数降低。HIV-MAG DNA疫苗经肌肉注射和电穿孔给药在所有剂量的IL-12 pDNA下都是安全的。该剂量的VSV-Gag疫苗与一些参与者的发热和病毒症状有关，但疫苗方案是安全的，通常耐受性良好。临床Trials.gov NCT 01578889。
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.
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影响因子：
4.2
作者：
Fuchs JD;Frank I;Elizaga ML;Allen M;Frahm N;Kochar N;Li S;Edupuganti S;Kalams SA;Tomaras GD;Sheets R;Pensiero M;Tremblay MA;Higgins TJ;Latham T;Egan MA;Clarke DK;Eldridge JH;HVTN 090 Study Group and the National Institutes of Allergy and Infectious Diseases HIV Vaccine Trials Network;Mulligan M;Rouphael N;Estep S;Rybczyk K;Dunbar D;Buchbinder S;Wagner T;Isbell R;Chinnell V;Bae J;Escamilla G;Tseng J;Fair R;Ramirez S;Broder G;Briesemeister L;Ferrara A
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