Absence of systemic toxicity changes following intramuscular administration of novel pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines to BALB/c mice
Absence of systemic toxicity changes following intramuscular administration of novel pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines to BALB/c mice
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DOI：
10.1016/j.vaccine.2013.06.068
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发表时间：
2013-11-12
期刊：
影响因子：
5.5
通讯作者：
Hanke, Tomag
中科院分区：
文献类型：
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作者：
Ondondo, Beatrice;Brennan, Caroline;Hanke, Tomag
背景资料：在雄性和雌性BALB/c小鼠的两次重复给药研究中，评价了表达源自HIV-1蛋白质组最保守区域的嵌合免疫原的三种候选HIV-1疫苗质粒pSG2.HIVconsv DNA（D）、ChAdV63.HIVconsv（C）和MVA.HIVconsv（M）的全身毒性。在研究UNO 011中，小鼠接受了3剂2 × 10（7）空斑形成单位的MVA.HIVconsv疫苗（MMM）。在研究UNO 012中，小鼠接受3剂50 μ g pSG2.HIVconsv DNA，随后接受单剂5.95 × 10（9）个病毒颗粒的ChAdV63.HIVconsv疫苗（DDDC）。相似构成的对照组仅接受相同体积剂量的溶剂（磷酸盐缓冲盐水）。所有疫苗均以14天的间隔通过右后肢肌肉注射针注射给药，并在末次给药后7天处死动物。进行局部和全身毒性评估。确认了诱导HIV-1特异性应答。评估的参数包括临床状况，体重，食物消耗，检眼镜，血液学，血液化学，器官重量和宏观和微观pathology.Results：在这两项研究中，治疗与候选疫苗引起强烈的HIV-1特异性T细胞反应。疫苗治疗耐受性良好，无任何不良全身毒理学变化。在这些研究中观察到的局部毒性结果是一致的预测响应的疫苗/物质管理通过肌肉注射injection.Conclusions：三种新的抗HIV-1疫苗的耐受性良好，当肌肉注射给BALB/c小鼠。这些结果支持了英国药品和保健产品管理局的授权申请，以在健康的未感染受试者和抗逆转录病毒治疗稳定的HIV-1感染患者中首次在I期临床试验中测试这些疫苗。(C)2013作者由爱思唯尔有限公司出版。保留所有权利。
Background: The systemic toxicity of three candidate HIV-1 vaccines plasmid pSG2.HIVconsv DNA (D), ChAdV63.HIVconsv (C) and MVA.HIVconsv (M) expressing chimeric immunogen derived from the most conserved regions of the HIV-1 proteome was evaluated in two repeat-dose studies in the male and female BALB/c mice.Methods: In study UNO011, mice received three doses of 2 x 10(7) plaque-forming units of MVA.HIVconsv vaccine (MMM). In study UNO012, mice received 3 doses of 50 mu g of pSG2.HIVconsv DNA followed by a single dose of 5.95 x 10(9) virus particles of ChAdV63.HIVconsv vaccine (DDDC). Similarly constituted control groups received the vehicle alone (phosphate buffered saline) at the same volume-dose. All vaccines were administered by intramuscular needle injection into the right hind limb at 14-day intervals and animals were sacrificed 7 days after the last dose. Assessment of local and systemic toxicity was made. Induction of HIV-1-specific responses was confirmed. Parameters assessed included clinical condition, body weight, food consumption, ophthalmoscopy, haematology, blood chemistry, organ weight and macroscopic and microscopic pathology.Results: In both studies, treatment with the candidate vaccines elicited strong HIV-1-specific T-cell responses. The vaccine treatment was well-tolerated without any adverse systemic toxicological changes. The local toxicity findings observed in these studies were consistent with the predicted response to a vaccine/substance administration by intramuscular injection.Conclusions: The three novel anti-HIV-1 vaccines were well tolerated when administered by intramuscular injection to BALB/c mice. These results supported an application for authorisation by the Medicines and Healthcare Products Regulatory Agency of the UK to test these vaccines for the first time in phase I clinical trials in healthy both uninfected subjects and HIV-1-infected patients stable on antiretroviral treatment. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.