Alzheimer's disease Advax(CpG)-adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and A beta pathological molecules

作者：Davtyan Hayk; Zagorski Karen; Rajapaksha Harinda; Hovakimyan Armine; Davtyan Arpine; Petrushina Irina; Kazarian Konstantin; Cribbs David H; Petrovsky Nikolai; Agadjanyan Michael G^*; Ghochikyan Anahit^*

来源：Scientific Reports, 2016, 6(1): 28912.

DOI：10.1038/srep28912

Although beta-amyloid (A beta) may be the primary driver of Alzheimer's disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting A beta and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting A beta (AV-1959R), Tau (AV-1980R) or A beta/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel (R), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, A beta and tau pathological molecules. While anti-A beta antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing preclinical assessment and future human clinical trials.

• 出版日期2016-7-1