A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates.
A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates.
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DOI：
10.2174/1566523214666140522122633
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发表时间：
2014
影响因子：
3.6
通讯作者：
Hooper JW
中科院分区：
文献类型：
--
作者：
Kwilas S;Kishimori JM;Josleyn M;Jerke K;Ballantyne J;Royals M;Hooper JW
新诺布雷病毒(SNV)和安第斯病毒(ANDV)分别是北美和南美洲汉坦病毒肺综合征(HPS)病例的主要原因。患者在HPS中存活的可能性只有三分之二。此前，我们证明了编码病毒包膜糖蛋白的SNV和ANDV DNA疫苗在实验室动物和(ANDV)非人类灵长类动物(NHP)中都能诱导出高滴度的中和抗体。在这些研究中，疫苗是通过基因枪或肌肉电穿孔传递的。在这里，我们测试了使用一次性注射器喷射(DSJI)系统(PharmaJet，Inc.)是否可以有效地提供SNV/ANDV DNA疫苗(HPS DNA疫苗)。PharmaJet肌肉内(IM)和皮内(ID)无针设备是FDA 510(K)批准的，使用简单，不需要电力或加压气体。首先，我们测试了由PharmaJet IM或ID设备提供的SNV DNA疫苗在兔和NHP中的效果。IM和ID装置均能在兔和NHP中产生高效价的抗SNV中和抗体反应。然而，ID设备需要在NHP中至少接种两次疫苗才能检测大多数动物的中和抗体，而所有使用IM设备血清转换的动物接种一次疫苗。由于IM设备在NHP中更有效，因此选择Stratis®(PharmaJet IM设备)进行后续研究。我们评估了使用Stratis®交付的HPS DNA疫苗，发现它在兔(n=8/组)中产生了高效价的抗SNV和抗ANDV中和抗体，通过经典的空斑减少中和试验和一种新的假病毒中和试验进行了检测。我们感兴趣的是确定双链疫苗注射(例如，通过组织的高速液体渗透)与其他疫苗注射方法(如针头/注射器)之间的差异是否可能导致更具免疫原性的DNA疫苗。为了实现这一点，我们比较了由DSJI提供的HPS DNA疫苗与NHP中的针头/注射器(n=8/组)。结果发现，三联疫苗免疫组的抗新城疫病毒和抗新城疫病毒中和抗体效价均显著高于针管组(p值均为0.0115)。例如，在接种疫苗组中，抗SNV和抗ANDV的PRNT50几何平均滴度(GMT)分别为1,974和349，而针头/注射器组分别为87和42。这些数据首次证明，由弹簧驱动的dsji装置能够有效地将DNA疫苗输送到nnp。无论是这种HPS DNA疫苗，还是由弹簧动力的DSJI提供的任何DNA疫苗，都需要临床试验才能在人类身上引起强烈的免疫反应。
Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis® (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis® and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found that both the anti-SNV and anti-ANDV neutralizing antibody titers were significantly higher (p-value 0.0115) in the DSJI-vaccinated groups than the needle/syringe group. For example, the anti-SNV and anti-ANDV PRNT50 geometric mean titers (GMTs) were 1,974 and 349 in the DSJI-vaccinated group versus 87 and 42 in the needle/syringe group. These data demonstrate, for the first time, that a spring-powered DSJI device is capable of effectively delivering a DNA vaccine to NHPs. Whether this HPS DNA vaccine, or any DNA vaccine, delivered by spring-powered DSJI will elicit a strong immune response in humans, requires clinical trials.