Hovakimyan Armine, Chilingaryan Garri, King Olga, Capocchi Joia Kai, Chadarevian Jean Paul, Davtyan Hayk, Kniazev Roman, Agadjanyan Michael G, Ghochikyan Anahit
The Institute for Molecular Medicine, Huntington Beach, CA 92647, USA.
The Institute for Memory Impairments and Neurological Disorders, The University of California, Irvine, CA 92697, USA.
Vaccines (Basel). 2024 Jun 14;12(6):659. doi: 10.3390/vaccines12060659.
The escalating global healthcare challenge posed by Alzheimer's Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D.
阿尔茨海默病(AD)给全球医疗保健带来的挑战不断升级,且由于缺乏有效治疗方法而愈发严重,这凸显了采用创新方法对抗这种毁灭性疾病的迫切需求。目前,被动免疫疗法和主动免疫疗法仍然是治疗AD最具前景的策略。美国食品药品监督管理局(FDA)批准的lecanemab可显著减少早期AD患者大脑中的β淀粉样蛋白(Aβ)聚集体,这些患者每两周接受一次这种人源化单克隆抗体治疗。尽管这些试验中观察到的临床益处并不显著,但研究人员强调了预防性免疫疗法的重要性。重要的是,免疫疗法研究的数据表明,接种疫苗者外周血中的抗体浓度应足以靶向中枢神经系统中的Aβ。为了在有AD风险的接种疫苗者体内产生相对较高浓度的抗体,我们开发了一个通用疫苗平台MultiTEP,并在此基础上开发了一种靶向病理性Aβ的DNA疫苗AV-1959D,完成了支持研究性新药申请(IND)的研究,并启动了一项针对早期AD志愿者的I期临床试验。我们目前的初步研究将先进的MultiTEP技术与一种新型mRNA方法相结合,开发了一种包裹在脂质纳米颗粒(LNP)中的mRNA疫苗AV-1959LR。在此,我们报告1959LR在小鼠和非人灵长类动物中的免疫原性初步研究结果,并将其与DNA对应物AV-1959D的免疫原性进行比较。