Homologous Boosting with Adenoviral Serotype 5 HIV Vaccine (rAd5) Vector Can Boost Antibody Responses despite Preexisting Vector-Specific Immunity in a Randomized Phase I Clinical Trial

BackgroundNeedle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.MethodsThirty-one adults, 18–55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.ResultsOverall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boost.ConclusionsBiojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Trial RegistrationClinicaltrials.gov NCT00709605 NCT00709605【背景】无针给药可提升DNA疫苗的免疫原性，但同时也会伴随更显著的局部不良反应。本研究首次对比了Biojector无针给药（Biojector）与传统针头给药方式在重组腺病毒5型（recombinant adenovirus type 5, rAd5）HIV候选疫苗接种中的应用效果。 【方法】本项Ⅰ期开放标签临床试验中，31名年龄介于18至55岁的成年人被随机分组，其中20名未接触过rAd5疫苗的受试者、11名曾接种rAd5疫苗的受试者，均接受单次剂量为1010 PU的rAd5疫苗肌内注射（intramuscular, IM），给药方式分为传统针头注射与Biojector无针给药。研究人员对受试者进行了为期5天的主动征集不良反应（solicited reactogenicity）记录；临床安全性与免疫原性随访持续至接种后24周。 【结果】总体而言，两种给药方式的注射均具有良好耐受性，未出现严重不良事件。Biojector组的任意局部不良反应发生率为16/16（100%），针头注射组为11/15（73%）。Biojector与针头给药方式在HIV包膜蛋白（Env）特异性抗体应答方面无显著差异。无论初免与加强免疫的间隔时长如何，接受rAd5疫苗加强剂量的受试者，其Env特异性抗体应答水平均较单次接种（无论采用何种给药方式）高出10倍以上。 【结论】相较于传统针头给药，Biojector无针给药并未提升rAd5疫苗的抗体应答水平。尽管受试者已存在针对载体的预存免疫，采用同源rAd5基因载体进行加强免疫，仍可增强插入片段特异性的抗体应答。 【试验注册】Clinicaltrials.gov NCT00709605 NCT00709605