Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
School of Chemistry, Tiangong University, Tianjin 300387, China.
Acta Biomater. 2022 Oct 1;151:491-500. doi: 10.1016/j.actbio.2022.08.006. Epub 2022 Aug 7.
Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.
目前的疫苗接种计划，包括 COVID-19 疫苗，需要多次接种。人们非常希望能够有一种只需要注射一次就能产生等效免疫反应的疫苗。不幸的是，由于非常规的释放动力学难以实现，这仍然是一个巨大的挑战。在此，我们设计了一种基于高度可编程的动态层层（LBL）膜释放系统的单次注射 COVID-19 疫苗。抗原，SARS-CoV-2 刺突蛋白的 S1 亚单位，被加载到碳酸钙微球中，然后用单宁酸（TA）/聚乙二醇（PEG）LBL 膜进一步包裹。通过混合涂覆不同厚度 TA/PEG 膜的微球获得了单次注射疫苗。由于 TA/PEG 涂层具有独特的恒速侵蚀行为，该系统允许抗原进行明显的多次脉冲释放，这种释放模式与传统多剂量疫苗中的抗原释放模式非常相似。在小鼠中进行单次注射疫苗免疫可诱导强烈和持久的 S1 特异性体液和细胞免疫反应。来自接种动物的血清在体外具有强大的病毒中和能力。更重要的是，单次注射疫苗诱导的免疫反应和病毒抑制与相应的多剂量疫苗一样强烈，因为它们具有相同的抗原释放模式。
疫苗是对抗 COVID-19 等传染病最强大和最具成本效益的武器。然而，目前的疫苗接种计划，包括 COVID-19 疫苗，需要多次接种。在此，我们设计了一种基于高度可编程的释放系统的单次注射 COVID-19 疫苗。这种疫苗以脉冲方式释放抗原，这种释放模式与传统多剂量疫苗中的抗原释放模式非常相似。因此，单次注射新疫苗可诱导与相应多剂量疫苗接种方案相似的免疫反应和病毒抑制。
