Muller David A, Depelsenaire Alexandra C I, Shannon Ashleigh E, Watterson Daniel, Corrie Simon R, Owens Nick S, Agyei-Yeboah Christiana, Cheung Stacey T M, Zhang Jin, Fernando Germain J P, Kendall Mark A F, Young Paul R
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
Vaccines (Basel). 2019 Nov 20;7(4):189. doi: 10.3390/vaccines7040189.
Dengue virus is the most important arbovirus impacting global human health, with an estimated 390 million infections annually, and over half the world's population at risk of infection. While significant efforts have been made to develop effective vaccines to mitigate this threat, the task has proven extremely challenging, with new approaches continually being sought. The majority of protective, neutralizing antibodies induced during infection are targeted by the envelope (E) protein, making it an ideal candidate for a subunit vaccine approach. Using truncated, recombinant, secreted E proteins (sE) of all 4 dengue virus serotypes, we have assessed their immunogenicity and protective efficacy in mice, with or without Quil-A as an adjuvant, and delivered via micropatch array (MPA) to the skin in comparison with more traditional routes of immunization. The micropatch contains an ultra-high density array (21,000/cm) of 110 μm microprojections. Mice received 3 doses of 1 μg (nanopatch, intradermal, subcutaneous, or intra muscular injection) or 10 μg (intradermal, subcutaneous, or intra muscular injection) of tetravalent sE spaced 4 weeks apart. When adjuvanted with Quil-A, tetravalent sE vaccination delivered via MPA resulted in earlier induction of virus-neutralizing IgG antibodies for all four serotypes when compared with all of the other vaccination routes. Using the infectious dengue virus AG129 mouse infectious dengue model, these neutralizing antibodies protected all mice from lethal dengue virus type 2 D220 challenge, with protected animals showing no signs of disease or circulating virus. If these results can be translated to humans, MPA-delivered sE represents a promising approach to dengue virus vaccination.
登革病毒是影响全球人类健康的最重要虫媒病毒，估计每年有3.9亿人感染，全球超过一半的人口有感染风险。尽管已经做出了巨大努力来开发有效的疫苗以减轻这一威胁，但事实证明这项任务极具挑战性，仍在不断寻求新的方法。感染期间诱导产生的大多数保护性中和抗体都以包膜（E）蛋白为靶点，这使其成为亚单位疫苗方法的理想候选对象。我们使用了所有4种登革病毒血清型的截短重组分泌型E蛋白（sE），评估了它们在小鼠体内的免疫原性和保护效力，有无佐剂Quil-A，并与更传统的免疫途径相比，通过微贴片阵列（MPA）递送至皮肤。微贴片包含一个超高密度阵列（21,000个/平方厘米）的110μm微突起。小鼠接受3剂1μg（纳米贴片、皮内、皮下或肌肉注射）或10μg（皮内、皮下或肌肉注射）的四价sE，间隔4周。当与Quil-A佐剂联合使用时，与所有其他免疫途径相比，通过MPA递送的四价sE疫苗接种能更早诱导出针对所有四种血清型的病毒中和IgG抗体。使用感染性登革病毒AG129小鼠感染性登革模型，这些中和抗体保护所有小鼠免受致命的2型登革病毒D220攻击，受保护的动物没有疾病迹象或循环病毒。如果这些结果能够转化到人类身上，MPA递送的sE代表了一种有前景的登革病毒疫苗接种方法。
