Technological challenges in the preclinical development of an HIV nanovaccine candidate
Technological challenges in the preclinical development of an HIV nanovaccine candidate
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DOI：
10.1007/s13346-020-00721-8
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发表时间：
2020-02-10
影响因子：
5.4
通讯作者：
Crecente-Campo, Jose
中科院分区：
文献类型：
--
作者：
Dacoba, Tamara G.;Ruiz-Gaton, Luisa;Crecente-Campo, Jose
尽管纳米医学领域的研究非常活跃，但只有少数基于纳米的药物递送系统已经进入市场。研究和商业化之间的“死亡谷”部分归因于纳米制剂的有限表征和再现性。我们的研究小组先前已经报道了基于肽的纳米疫苗候选物用于预防猕猴中SIV感染的潜力。该候选疫苗由含有12种SIV肽抗原的壳聚糖/硫酸葡聚糖纳米颗粒组成。这项工作的目的是严格表征这些含有特定肽的纳米制剂之一，遵循质量设计方法。不同的质量属性的评价进行了几个互补的技术，如动态光散射，纳米粒子跟踪分析，和电子显微镜粒度表征。由三个独立实验室验证了批间重现性。最后，对制造技术的长期稳定性和可扩展性进行了评估。总的来说，这些数据以及在猕猴中获得的体内有效性结果强调了这种新疫苗在临床试验中的前景。图形摘要
Despite a very active research in the field of nanomedicine, only a few nano-based drug delivery systems have reached the market. The "death valley" between research and commercialization has been partially attributed to the limited characterization and reproducibility of the nanoformulations. Our group has previously reported the potential of a peptide-based nanovaccine candidate for the prevention of SIV infection in macaques. This vaccine candidate is composed of chitosan/dextran sulfate nanoparticles containing twelve SIV peptide antigens. The aim of this work was to rigorously characterize one of these nanoformulations containing a specific peptide, following a quality-by-design approach. The evaluation of the different quality attributes was performed by several complementary techniques, such as dynamic light scattering, nanoparticle tracking analysis, and electron microscopy for particle size characterization. The inter-batch reproducibility was validated by three independent laboratories. Finally, the long-term stability and scalability of the manufacturing technique were assessed. Overall, these data, together with the in vivo efficacy results obtained in macaques, underline the promise this new vaccine holds with regard to its translation to clinical trials.Graphical abstract