Epitope-based DNA vaccine for Alzheimer's disease: translational study in macaques

基于表位的阿尔茨海默病 DNA 疫苗:猕猴转化研究

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作者:Claire F Evans, Hayk Davtyan, Irina Petrushina, Armine Hovakimyan, Arpine Davtyan, Drew Hannaman, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan

Background

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.

Conclusions

This translational study demonstrates that a DNA-based epitope vaccine for AD could be appropriate for human clinical testing.

Methods

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.

Results

AV-1955 generates long-term, potent anti-Aβ antibodies and cellular immune responses specific to foreign T-helper epitopes but not to self-Aβ. Conclusions: This translational study demonstrates that a DNA-based epitope vaccine for AD could be appropriate for human clinical testing.

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