无针注射装置递送的 DNA 疫苗可提高经 rAd5 加强后针对抗体和 CD8+ T 细胞应答的初免效力：一项随机临床试验。
DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial.
机构信息
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
出版信息
PLoS One. 2013;8(4):e59340. doi: 10.1371/journal.pone.0059340. Epub 2013 Apr 8.
BACKGROUND
DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.
METHODS
Forty adults, 18-50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody.
RESULTS
120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.
CONCLUSIONS
DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00109629.
背景
DNA 疫苗的免疫原性受到低效传递的限制。使用 CO2 驱动的 Biojector®装置进行无针 DNA 传递，并将其与针和注射器的传递进行了比较，评估了安全性和免疫原性。
方法
40 名 18-50 岁的成年人，随机分配接受肌肉内（IM）接种 DNA 疫苗 VRC-HIVDNA016-00-VP（0、4、8 周），使用 Biojector®2000™ 或针和注射器（N/S），并在第 24 周用 N/S 接种 VRC-HIVADV014-00-VP（rAd5）进行加强免疫，接种剂量为 10（10）或 10（11）个病毒颗粒单位（PU）。根据分配方案，每个方案的人数相等，预先存在的 Ad5 中和抗体滴度较低（≤500）或较高（>500）。
结果
共进行了 120 次 DNA 和 39 次 rAd5 注射，36 名受试者完成了随访研究样本采集。在第 28 周（rAd5 加强免疫后 4 周），Biojector®组和 N/S 组的 IFN-γ ELISpot 反应率分别为 17/19（89%）和 13/17（76%）。Biojector®组的 ELISpot 反应幅度比 N/S 组高约 3 倍。通过 ICS 观察到对 CD8+T 细胞反应的速率和幅度也有类似的影响，但对 CD4+T 细胞反应没有影响。Biojector 引发的受试者中，Env 特异性抗体反应约高 10 倍。
结论
Biojector®接种 DNA 疫苗耐受性良好，与针注射相比，在接受 rAd5 加强免疫后，引发更高的 IFN-γ ELISpot、CD8+T 细胞和抗体反应。
试验注册
ClinicalTrials.gov NCT00109629。
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