Nonhuman Primates Are Protected against Marburg Virus Disease by Vaccination with a Vesicular Stomatitis Virus Vector-Based Vaccine Prepared under Conditions to Allow Advancement to Human Clinical Trials.
Nonhuman Primates Are Protected against Marburg Virus Disease by Vaccination with a Vesicular Stomatitis Virus Vector-Based Vaccine Prepared under Conditions to Allow Advancement to Human Clinical Trials.
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DOI：
10.3390/vaccines10101582
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发表时间：
2022-09-21
期刊：
影响因子：
7.8
通讯作者：
Parks CL
中科院分区：
文献类型：
--
作者：
Cooper CL;Morrow G;Yuan M;Coleman JW;Hou F;Reiserova L;Li SL;Wagner D;Carpov A;Wallace-Selman O;Valentin K;Choi Y;Wilson A;Kilianski A;Sayeed E;Agans KN;Borisevich V;Cross RW;Geisbert TW;Feinberg MB;Gupta SB;Parks CL
需要疫苗来破坏或预防整个西非和中非人类丝状病毒的持续爆发，包括马尔堡病毒（MARV）的爆发。作为丝状病毒疫苗产品开发计划的一部分，重要的是在临床前开发早期研究剂量反应，以确定安全性、免疫原性和有效性可能最佳的剂量范围，并可能证明使用较低剂量是可行的，这将改善产品的可及性。为了确定编码MARV糖蛋白（GP）的生产就绪型重组水泡性口炎病毒活疫苗载体（rVSV EPOG-MARV-GP）的有效剂量范围，在食蟹猴中进行了剂量范围研究。结果表明，单次肌内注射200个空斑形成单位（PFU）对致死率100%有效，并可预防与MARV安哥拉感染相关的病毒血症和临床病理学的发展。在测试的疫苗剂量中，存在接近2000倍范围的抗MARV糖蛋白（GP）血清IgG滴度，即使在最低剂量下也可检测到血清转化。在接种较高疫苗剂量的动物中也检测到病毒中和血清抗体，表明疫苗接种诱导了功能性抗体，但该试验是血清转化的灵敏度较低的指标。总的来说，数据表明在免受疾病影响的动物中观察到相对宽范围的抗GP血清IgG滴度，这意味着血清转化与功效正相关，但是，对从我们的研究以及未来的临床前研究中收集的样本进行更广泛的免疫学分析，将有助于确定与保护相关的其他免疫应答，这些免疫应答可作为监测人类免疫应答的标志物。需要进行试验，以产生可支持未来疫苗许可证的数据。
Vaccines are needed to disrupt or prevent continued outbreaks of filoviruses in humans across Western and Central Africa, including outbreaks of Marburg virus (MARV). As part of a filovirus vaccine product development plan, it is important to investigate dose response early in preclinical development to identify the dose range that may be optimal for safety, immunogenicity, and efficacy, and perhaps demonstrate that using lower doses is feasible, which will improve product access. To determine the efficacious dose range for a manufacturing-ready live recombinant vesicular stomatitis virus vaccine vector (rVSV∆G-MARV-GP) encoding the MARV glycoprotein (GP), a dose-range study was conducted in cynomolgus macaques. Results showed that a single intramuscular injection with as little as 200 plaque-forming units (PFUs) was 100% efficacious against lethality and prevented development of viremia and clinical pathologies associated with MARV Angola infection. Across the vaccine doses tested, there was nearly a 2000-fold range of anti-MARV glycoprotein (GP) serum IgG titers with seroconversion detectable even at the lowest doses. Virus-neutralizing serum antibodies also were detected in animals vaccinated with the higher vaccine doses indicating that vaccination induced functional antibodies, but that the assay was a less sensitive indicator of seroconversion. Collectively, the data indicates that a relatively wide range of anti-GP serum IgG titers are observed in animals that are protected from disease implying that seroconversion is positively associated with efficacy, but that more extensive immunologic analyses on samples collected from our study as well as future preclinical studies will be valuable in identifying additional immune responses correlated with protection that can serve as markers to monitor in human trials needed to generate data that can support vaccine licensure in the future.
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影响因子：
7.8
作者：
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