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
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
复制标题
DOI：
10.1371/journal.pone.0059340
复制
发表时间：
2013-04-08
期刊：
影响因子：
3.7
通讯作者：
Nabel, Gary J.
中科院分区：
文献类型：
--
作者：
Graham, Barney S.;Enama, Mary E.;Nabel, Gary J.
背景：DNA疫苗的免疫原性一直受到递送效率低下的限制。使用二氧化碳驱动的生物喷射器(R)装置无针递送DNA与针头和注射器递送DNA进行比较，并评估其安全性和免疫原性。方法：选取40名18-50岁的成年人，随机分配于第0、4、8周分别用生物注射器（TM）或针筒（N/S）注射DNA疫苗VRC-HIVDNA016-00-VP进行肌肉注射（IM），第24周用N/S分别为10（10）或10（11）粒单位（PU）的VRC-HIVADV014-00-VP （rAd5）增强IM。在每个指定的时间表中，相同数量的人先前存在的Ad5中和抗体的倒数滴度较低（500）。结果：注射DNA 120例，注射rAd5 39例；36名受试者完成了后续研究样本收集。IFN-gamma ELISpot在第28周（rAd5增强后4周），Biojector (R)的应答率为17/19 (89%)，N/S递送的应答率为13/17（76%）。与N/S组相比，Biojector (R)的ELISpot反应幅度约为3倍。ICS对CD8+ t细胞应答率和强度的影响相似，但对CD4+ t细胞应答没有影响。在生物喷射器启动的受试者中，env特异性抗体反应大约高出10倍。结论：与针头注射相比，生物注射器(R)的DNA疫苗耐受性良好，在rAd5增强后，ifn - γ ELISpot， CD8+ t细胞和抗体反应增强。试验注册：ClinicalTrials.gov NCT00109629
Background: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector (R) 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 (R) 2000 (TM) 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) 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-gamma ELISpot response rates were 17/19 (89%) for Biojector (R) 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 (R) 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 (R) was well-tolerated and compared to needle injection, primed for greater IFN-gamma ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.Trial Registration: ClinicalTrials.gov NCT00109629