Garcia-Valtanen Pablo, Yeow Arthur E L, Mekonnen Zelalem A, Whelan Dawn M, Santos Ryan, Al-Delfi Zahraa, Rodrigues Susana, Gavan Pauline, Howard Keith, Masavuli Makutiro G, Grubor-Bauk Branka
Viral Immunology Group, Discipline of Surgery, The Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, SA 5011, Australia.
Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Universidad Miguel Hernández, 03202 Elche, Spain.
Mol Ther Nucleic Acids. 2025 Jul 17;36(3):102628. doi: 10.1016/j.omtn.2025.102628. eCollection 2025 Sep 9.
The coronavirus disease 2019 pandemic has highlighted the critical need for thermostable vaccines to ensure equitable distribution and accessibility, particularly in regions lacking cold chain infrastructure. Here we present a thermostable, solid dose DNA vaccine (SDV) platform for subcutaneous delivery, based on a sugar-sugar alcohol-polymer formulation manufactured via lyophilization and compaction. Using luciferase-expressing plasmid as a model, we demonstrate that subcutaneous vaccination with SDV formulation of C57BL/6 mice results in efficient and durable transgene expression . stability assays confirmed that the SDV formulation maintained excellent thermostability after 30 days of storage at 4°C, 25°C, 37°C, and 42°C. We next applied the SDV platform to a Zika virus (ZIKV) NS1 DNA vaccine and immunized BALB/c mice. ZIKV-SDV vaccination elicited robust NS1-specific antibody and T cell responses, and conferred protection upon ZIKV challenge. These data establish the feasibility of lyophilized SDV DNA vaccines for needle-free thermostable delivery. By eliminating the need for reconstitution, refrigeration, and skilled administration, SDV formulation has the potential to enhance the deployment, cost effectiveness, and shelf-life of DNA vaccines in resource-limited settings.
2019年冠状病毒病大流行凸显了对热稳定疫苗的迫切需求，以确保公平分配和可及性，特别是在缺乏冷链基础设施的地区。在此，我们展示了一种用于皮下给药的热稳定固体剂量DNA疫苗（SDV）平台，该平台基于通过冻干和压片制造的糖-糖醇-聚合物配方。使用表达荧光素酶的质粒作为模型，我们证明用SDV配方对C57BL/6小鼠进行皮下接种可导致高效且持久的转基因表达。稳定性测定证实，SDV配方在4°C、25°C、37°C和42°C储存30天后仍保持出色的热稳定性。接下来，我们将SDV平台应用于寨卡病毒（ZIKV）NS1 DNA疫苗，并免疫BALB/c小鼠。ZIKV-SDV疫苗接种引发了强烈的NS1特异性抗体和T细胞反应，并在ZIKV攻击时提供了保护。这些数据证实了冻干SDV DNA疫苗用于无针热稳定给药的可行性。通过消除重构、冷藏和熟练给药的需求，SDV配方有可能提高DNA疫苗在资源有限环境中的部署、成本效益和保质期。
