Turvey Michelle E, Uppu Divakara S S M, Mohamed Sharif Abdul Rahim, Bidet Katell, Alonso Sylvie, Ooi Eng Eong, Hammond Paula T
Infectious Diseases IRG Singapore-MIT Alliance for Research and Technology Singapore.
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, Immunology Programme Life Sciences Institute, National University of Singapore Singapore.
Bioeng Transl Med. 2019 Feb 25;4(2):e10127. doi: 10.1002/btm2.10127. eCollection 2019 May.
Current live-attenuated dengue vaccines require strict cold chain storage. Methods to preserve dengue virus (DENV) viability, which enable vaccines to be transported and administered at ambient temperatures, will be decisive towards the implementation of affordable global vaccination schemes with broad immunization coverage in resource-limited areas. We have developed a microneedle (MN)-based vaccine platform for the stabilization and intradermal delivery of live DENV from minimally invasive skin patches. Dengue virus-stabilized microneedle arrays (VSMN) were fabricated using saccharide-based formulation of virus and could be stored dry at ambient temperature up to 3 weeks with maintained virus viability. Following intradermal vaccination, VSMN-delivered DENV was shown to elicit strong neutralizing antibody responses and protection from viral challenge, comparable to that of the conventional liquid vaccine administered subcutaneously. This work supports the potential for MN-based dengue vaccine technology and the progression towards cold chain-independence. Dengue virus can be stabilized using saccharide-based formulations and coated on microneedle array vaccine patches for storage in dry state with preserved viability at ambient temperature (VSMN; virus-stabilized microneedle arrays).
目前的减毒活登革热疫苗需要严格的冷链储存。能够使疫苗在常温下运输和接种的登革热病毒(DENV)存活保存方法,对于在资源有限地区实施具有广泛免疫覆盖的可负担得起的全球疫苗接种计划将起到决定性作用。我们开发了一种基于微针(MN)的疫苗平台,用于从微创皮肤贴片稳定并皮内递送活DENV。使用基于糖类的病毒制剂制备了登革热病毒稳定微针阵列(VSMN),其可在常温下干燥储存长达3周,同时保持病毒活性。皮内接种后,VSMN递送的DENV显示出能引发强烈的中和抗体反应并提供针对病毒攻击的保护,与皮下注射的传统液体疫苗相当。这项工作支持了基于微针的登革热疫苗技术的潜力以及向无需冷链方向的发展。登革热病毒可以使用基于糖类的制剂进行稳定,并包被在微针阵列疫苗贴片上,以便在常温下以干燥状态储存并保持活性(VSMN;病毒稳定微针阵列)。