TY - JOUR
T1 - Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates
AU - Hovakimyan, Armine
AU - Zagorski, Karen
AU - Chailyan, Gor
AU - Antonyan, Tatevik
AU - Melikyan, Levon
AU - Petrushina, Irina
AU - Batt, Dash G.
AU - King, Olga
AU - Ghazaryan, Manush
AU - Donthi, Aashrit
AU - Foose, Caitlynn
AU - Petrovsky, Nikolai
AU - Cribbs, David H.
AU - Agadjanyan, Michael G.
AU - Ghochikyan, Anahit
PY - 2022/10/12
Y1 - 2022/10/12
N2 - Pathological forms of Tau protein are directly associated with neurodegeneration and correlate with Alzheimer’s Disease (AD) symptoms, progression, and severity. Previously, using various mouse models of Tauopathies and AD, we have demonstrated the immunogenicity and efficacy of the MultiTEP-based adjuvanted vaccine targeting the phosphatase activating domain (PAD) of Tau, AV-1980R/A. Here, we analyzed its immunogenicity in non-human primates (NHP), the closest phylogenic relatives to humans with a similar immune system, to initiate the transition of this vaccine into clinical trials. We have demonstrated that AV-1980R/A is highly immunogenic in these NHPs, activating a broad but unique to each monkey repertoire of MultiTEP-specific T helper (Th) cells that, in turn, activate B cells specific to PAD. The resulting anti-PAD IgG antibodies recognize pathological Tau tangles and Tau-positive neuritis in AD case brain sections with no staining in control non-AD cases. These published data and efficacy results support the AV-1980R/A vaccine progression to first-in-human clinical trials.
AB - Pathological forms of Tau protein are directly associated with neurodegeneration and correlate with Alzheimer’s Disease (AD) symptoms, progression, and severity. Previously, using various mouse models of Tauopathies and AD, we have demonstrated the immunogenicity and efficacy of the MultiTEP-based adjuvanted vaccine targeting the phosphatase activating domain (PAD) of Tau, AV-1980R/A. Here, we analyzed its immunogenicity in non-human primates (NHP), the closest phylogenic relatives to humans with a similar immune system, to initiate the transition of this vaccine into clinical trials. We have demonstrated that AV-1980R/A is highly immunogenic in these NHPs, activating a broad but unique to each monkey repertoire of MultiTEP-specific T helper (Th) cells that, in turn, activate B cells specific to PAD. The resulting anti-PAD IgG antibodies recognize pathological Tau tangles and Tau-positive neuritis in AD case brain sections with no staining in control non-AD cases. These published data and efficacy results support the AV-1980R/A vaccine progression to first-in-human clinical trials.
KW - Protein vaccines
KW - Alzheimer’s Disease (AD)
KW - MultiTEP-based adjuvanted vaccine
UR - http://www.scopus.com/inward/record.url?scp=85139764761&partnerID=8YFLogxK
U2 - 10.1038/s41541-022-00544-3
DO - 10.1038/s41541-022-00544-3
M3 - Article
AN - SCOPUS:85139764761
SN - 2059-0105
VL - 7
JO - npj Vaccines
JF - npj Vaccines
M1 - 117
ER -