Rothen Dominik A, Dutta Sudip Kumar, Krenger Pascal S, Pardini Alessandro, Vogt Anne-Cathrine S, Josi Romano, Lieknina Ilva, Osterhaus Albert D M E, Mohsen Mona O, Vogel Monique, Martina Byron, Tars Kaspars, Bachmann Martin F
Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland.
Department of Immunology RIA, University Hospital Bern, 3010 Bern, Switzerland.
Vaccines (Basel). 2024 Sep 14;12(9):1053. doi: 10.3390/vaccines12091053.
Declared as a Public Health Emergency in 2016 by the World Health Organization (WHO), the Zika virus (ZIKV) continues to cause outbreaks that are linked to increased neurological complications. Transmitted mainly by Aedes mosquitoes, the virus is spread mostly amongst several tropical regions with the potential of territorial expansion due to environmental and ecological changes. The ZIKV envelope protein's domain III, crucial for vaccine development due to its role in receptor binding and neutralizing antibody targeting, was integrated into sterically optimized AP205 VLPs to create an EDIII-based VLP vaccine. To increase the potential size of domains that can be accommodated by AP205, two AP205 monomers were fused into a dimer, resulting in 90 rather than 180 N-/C- termini amenable for fusion. EDIII displayed on AP205 VLPs has several immunological advantages, like a repetitive surface, a size of 20-200 nm (another PASP), and packaged bacterial RNA as adjuvants (a natural toll-like receptor 7/8 ligand). In this study, we evaluated a novel vaccine candidate for safety and immunogenicity in mice, demonstrating its ability to induce high-affinity, ZIKV-neutralizing antibodies without significant disease-enhancing properties. Due to the close genetical and structural characteristics, the same mosquito vectors, and the same ecological niche of the dengue virus and Zika virus, a vaccine covering all four Dengue viruses (DENV) serotypes as well as ZIKV would be of significant interest. We co-formulated the ZIKV vaccine with recently developed DENV vaccines based on the same AP205 VLP platform and tested the vaccine mix in a murine model. This combinatory vaccine effectively induced a strong humoral immune response and neutralized all five targeted viruses after two doses, with no significant antibody-dependent enhancement (ADE) observed. Overall, these findings highlight the potential of the AP205 VLP-based combinatory vaccine as a promising approach for providing broad protection against DENV and ZIKV infections. Further investigations and preclinical studies are required to advance this vaccine candidate toward potential use in human populations.
2016年，寨卡病毒（ZIKV）被世界卫生组织（WHO）宣布为突发公共卫生事件，该病毒持续引发疫情，且这些疫情与更多神经并发症相关。该病毒主要通过伊蚊传播，大多在几个热带地区扩散，由于环境和生态变化，存在地域扩张的可能性。寨卡病毒包膜蛋白的结构域III因其在受体结合和中和抗体靶向方面的作用，对疫苗开发至关重要，该结构域被整合到空间优化的AP205病毒样颗粒（VLP）中，以创建基于结构域III的VLP疫苗。为了增加AP205能够容纳的结构域的潜在大小，将两个AP205单体融合成一个二聚体，从而产生90个而非180个适合融合的N- / C-末端。展示在AP205 VLP上的结构域III具有多种免疫学优势，如重复的表面、20 - 200 nm的大小（另一种聚天冬氨酸）以及包装的细菌RNA作为佐剂（一种天然的Toll样受体7/8配体）。在本研究中，我们评估了一种新型候选疫苗在小鼠中的安全性和免疫原性，证明其能够诱导高亲和力、寨卡病毒中和抗体，且无明显的疾病增强特性。由于登革病毒和寨卡病毒在遗传和结构特征、传播媒介以及生态位方面相近，一种涵盖所有四种登革病毒（DENV）血清型以及寨卡病毒的疫苗将具有重大意义。我们将寨卡病毒疫苗与基于相同AP205 VLP平台最近开发的登革病毒疫苗共同配制，并在小鼠模型中测试了该疫苗组合。这种联合疫苗在两剂后有效地诱导了强烈的体液免疫反应，并中和了所有五种目标病毒，未观察到明显的抗体依赖性增强（ADE）。总体而言，这些发现突出了基于AP205 VLP的联合疫苗作为一种有前景的方法，可为预防登革病毒和寨卡病毒感染提供广泛保护的潜力。需要进一步的研究和临床前研究，以推动这种候选疫苗在人群中的潜在应用。
