Phase I Randomized Clinical Trial of VRC DNA and rAd5 HIV-1 Vaccine Delivery by Intramuscular (IM), Subcutaneous (SC) and Intradermal (ID) Administration (VRC 011)
收藏资源简介：
BackgroundPhase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (IM) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the IM, subcutaneous (SC) and intradermal (ID) routes of administration.MethodsSixty subjects were randomized to 6 schedules to evaluate the IM, SC or ID route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 IM boost (Wk24). DNA vaccine dosage was 4 mg IM or SC, but 0.4 mg ID, while all rAd5 vaccinations were 1010 PU. All injections were administered by needle and syringe.ResultsOverall, 27/30 subjects completed 3 DNA primes; 30/30 subjects completed rAd5 primes. Mild local pruritus (itchiness), superficial skin lesions and injection site nodules were associated with ID and SC, but not IM injections. All routes induced T-cell and antibody immune responses after rAd5 boosting. Overall, >95% had Env antibody and >80% had Env T-cell responses.ConclusionsThe pattern of local reactogenicity following ID and SC injections differed from IM injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following SC or ID delivery, supporting IM delivery as the preferred route of administration.Trial RegistrationClinicaltrials.gov NCT00321061
研究背景：针对肌内（intramuscular, IM）接种的VRC HIV DNA疫苗与rAd5疫苗开展的I期评估，为后续推进至IIb期效力研究提供了依据。本文报告了肌内、皮下（subcutaneous, SC）与皮内（intradermal, ID）三种疫苗接种途径的对比研究结果。 方法：本研究将60名受试者随机分为6组，以评估肌内、皮下或皮内途径作为初免接种的效果。其中3组采用DNA疫苗初免（分别于第0、4、8周接种），另外3组采用rAd5疫苗初免（于第0周接种）；所有组均在第24周接受肌内rAd5疫苗加强免疫。DNA疫苗的接种剂量为：肌内或皮下接种时4 mg，皮内接种时0.4 mg；所有rAd5疫苗接种剂量均为10^10 PU。所有接种均采用针头注射器完成。 结果：总体而言，30名受试者中有27名完成了3剂DNA疫苗初免；所有30名受试者均完成了rAd5疫苗初免。皮内与皮下接种者出现了轻度局部瘙痒（itchiness）、浅表皮肤损伤及接种部位结节，而肌内接种者未出现上述反应。所有接种途径在rAd5疫苗加强免疫后，均可诱导T细胞与抗体免疫应答。总体而言，超过95%的受试者产生了Env抗体应答，超过80%的受试者产生了Env T细胞应答。 结论：皮内与皮下接种后的局部反应原性特征与肌内接种存在差异，但所有接种途径均具有良好的耐受性。未发现皮下或皮内接种具备免疫原性优势的证据，因此支持肌内接种为优选的疫苗接种途径。 试验注册：ClinicalTrials.gov NCT00321061
