First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).
First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).
复制标题
对重组囊泡炎病毒的安全性和免疫原性的首次评估人类免疫缺陷病毒-1 GAG疫苗（HVTN 090）。
DOI：
10.1093/ofid/ofv082
复制
发表时间：
2015-09
影响因子：
4.2
通讯作者：
Ferrara A
中科院分区：
文献类型：
--
作者：
Fuchs JD;Frank I;Elizaga ML;Allen M;Frahm N;Kochar N;Li S;Edupuganti S;Kalams SA;Tomaras GD;Sheets R;Pensiero M;Tremblay MA;Higgins TJ;Latham T;Egan MA;Clarke DK;Eldridge JH;HVTN 090 Study Group and the National Institutes of Allergy and Infectious Diseases HIV Vaccine Trials Network;Mulligan M;Rouphael N;Estep S;Rybczyk K;Dunbar D;Buchbinder S;Wagner T;Isbell R;Chinnell V;Bae J;Escamilla G;Tseng J;Fair R;Ramirez S;Broder G;Briesemeister L;Ferrara A
背景。 我们报告了高度减毒、具有复制能力的重组水泡性口炎病毒 (rVSV) 人类免疫缺陷病毒 (HIV)-1 疫苗的首次人体安全性和免疫原性评估。方法。 60 名未感染 HIV-1 的健康成年人参加了一项随机、双盲、安慰剂对照的剂量递增研究。 12 名参与者组成的小组接受了 5 种剂量水平的 rVSV HIV-1 gag 疫苗（4.6 × 103 至 3.4 × 107 颗粒形成单位）（N = 10/组）或安慰剂（N = 2/组），在 0 个月和 2 个月时通过双侧肌肉注射进行注射。安全性监测包括从血液、尿液、唾液和口腔病变拭子中进行 VSV 培养。评估了水疱性口炎病毒中和抗体、T 细胞免疫原性和 HIV-1 特异性结合抗体。结果。 局部和全身反应原性症状为轻度至中度，并随着剂量的增加而增加。未报告严重反应原性或与产品相关的严重不良事件，所有 rVSV 培养均为阴性。所有疫苗接种者在接种 2 次疫苗后均呈 VSV 血清阳性。在最高剂量的加强后，通过干扰素-γ酶联免疫斑点检测到 63% 的参与者出现了 gag 特异性 T 细胞反应。结论。 具有复制能力的减毒 rVSV gag 疫苗在健康成人中具有可接受的安全性。这种 rVSV 载体是一种很有前景的新疫苗平台，可用于开发对抗 HIV-1 和其他严重人类疾病的疫苗。
Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 103 to 3.4 × 107 particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results. Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions. An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases.