Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramuscular/intradermal routes
Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramuscular/intradermal routes
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DOI：
10.1089/10430340260201644
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发表时间：
2002-09-01
影响因子：
4.2
通讯作者：
Hoffman, SL
中科院分区：
文献类型：
--
作者：
Epstein, JE;Gorak, EJ;Hoffman, SL
引入新疫苗需要选择提供安全施用和所需免疫原性水平的递送系统。在健康志愿者中评价了通过针肌内（IM）、通过喷射注射IM（Biojector（R））或通过喷射注射IM/皮内（ID）施用的每月三次2.5 mg剂量的PfCSP DNA疫苗的安全性、耐受性和免疫原性。疫苗接种耐受性良好。不良事件主要是轻度的，并且仅限于注射部位（98%）。喷射注射（IM或ID）与每次免疫接种的不良事件约为针IM的两倍相关，但在研究期间进行的民意调查中强烈且一致地首选。没有志愿者具有临床显著的生化或血液学变化或可检测的抗dsDNA抗体。总之，注射恶性疟原虫环子孢子（PfCSP）DNA疫苗似乎是安全的，耐受性良好时，通过任何三种方式的交付。然而，尽管在动物模型中喷射注射和ID递送后抗体应答有所改善，但在DNA疫苗接种后，通过免疫荧光抗体试验（IFAT）或酶联免疫吸附试验（ELISA）在志愿者中未检测到抗体。
Introduction of a new vaccine requires choosing a delivery system that provides safe administration and the desired level of immunogenicity. The safety, tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA vaccine were evaluated in healthy volunteers as administered intramuscularly (IM) by needle, IM by jet injection (Biojector(R)) or IM/intradermally (ID) by jet injection. Vaccine administration was well-tolerated. Adverse events were primarily mild and limited to the site of injection (98%). Jet injections (either IM or ID) were associated with approximately twice as many adverse events per immunization as needle IM, but nevertheless were strongly and consistently preferred in opinion polls taken during the study. No volunteers had clinically significant biochemical or hematologic changes or detectable anti-dsDNA antibodies. In conclusion, the injection of Plasmodium falciparum circumsporozoite (PfCSP) DNA vaccine appeared to be safe and well-tolerated when administered by any of the three modes of delivery. However, despite improved antibody responses following both jet injection and ID delivery in animal models, no antibodies could be detected in volunteers by immunofluorescence antibody test (IFAT) or enzyme-linked immunosorbent assay (ELISA) after DNA vaccination.