Ichor Medical Systems, San Diego, CA, USA.
Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Alzheimers Dement. 2014 May;10(3):284-95. doi: 10.1016/j.jalz.2013.04.505. Epub 2013 Jul 31.
Clinical trials with passive and active Alzheimer's disease (AD) vaccines suggest that early interventions are needed for improvement of cognitive and/or functional performance in patients, providing impetus for the development of safe and immunologically potent active vaccines targeting amyloid β (Aβ). The AN-1792 trial has indicated that Aβ-specific T cells may be unsafe for humans; therefore, other vaccines based on small Aβ epitopes are undergoing preclinical and clinical testing.
Humoral and cellular immune responses elicited in response to a novel DNA epitope-based vaccine (AV-1955) delivered to rhesus macaques using the TriGrid electroporation device were evaluated. Functional activities of anti-Aβ antibodies generated in response to vaccination were assessed in vitro.
AV-1955 generates long-term, potent anti-Aβ antibodies and cellular immune responses specific to foreign T-helper epitopes but not to self-Aβ.
This translational study demonstrates that a DNA-based epitope vaccine for AD could be appropriate for human clinical testing.
针对阿尔茨海默病（AD）的被动和主动疫苗的临床试验表明，需要对患者进行早期干预，以提高认知和/或功能表现，这为开发针对淀粉样蛋白β（Aβ）的安全且免疫原性强的主动疫苗提供了动力。AN-1792 试验表明，Aβ 特异性 T 细胞对人类可能不安全；因此，其他基于小 Aβ 表位的疫苗正在进行临床前和临床试验。
使用 TriGrid 电穿孔装置向恒河猴递送新型 DNA 表位疫苗（AV-1955）后，评估针对其产生的体液和细胞免疫反应。评估针对疫苗接种产生的抗 Aβ 抗体的体外功能活性。
AV-1955 可产生针对外来 T 辅助表位的长效、强效抗 Aβ 抗体和细胞免疫反应，但不会产生针对自身 Aβ 的反应。
这项转化研究表明，针对 AD 的 DNA 表位疫苗可能适合进行人体临床试验。
