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2 results on '"T-cell mapping"'

1. MultiTEP platform–based DNA vaccines for alpha-synucleinopathies: preclinical evaluation of immunogenicity and therapeutic potency

Author

Davtyan, Hayk, Zagorski, Karen, Petrushina, Irina, Kazarian, Konstantin, Goldberg, Natalie RS, Petrosyan, Janet, Blurton-Jones, Mathew, Masliah, Eliezer, Cribbs, David H, Agadjanyan, Michael G, and Ghochikyan, Anahit

Subjects
Biomedical and Clinical Sciences, Immunology, Dementia, Neurodegenerative, Orphan Drug, Acquired Cognitive Impairment, Neurosciences, Lewy Body Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Prevention, Immunization, Immunotherapy, Brain Disorders, Parkinson's Disease, Biotechnology, Alzheimer's Disease, Vaccine Related, Alzheimer's Disease Related Dementias (ADRD), Aging, Rare Diseases, Genetics, 5.1 Pharmaceuticals, 3.4 Vaccines, Neurological, Animals, Antibodies, Epitopes, B-Lymphocyte, Female, Humans, Mice, Inbred C57BL, Mice, Transgenic, Neurodegenerative Diseases, T-Lymphocytes, Helper-Inducer, Vaccines, DNA, alpha-Synuclein, DNA vaccines, MultiTEP platform, Anti-alpha-synuclein antibodies, B-cell mapping, T-cell mapping, Immunogenicity, Therapeutic potency, Anti-α-synuclein antibodies, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

We have previously demonstrated that anti-beta amyloid DNA vaccine (AV-1959D) based on our proprietary MultiTEP platform technology is extremely immunogenic in mice, rabbits, and monkeys. Importantly, MultiTEP platform enables development of vaccines targeting pathological molecules involved in various neurodegenerative disorders. Taking advantage of the universality of MultiTEP platform, we developed DNA vaccines targeting 3 B-cell epitopes (amino acids [aa]85-99, aa109-126, and aa126-140) of human alpha-synuclein (hα-Syn) separately or all 3 epitopes simultaneously. All 4 DNA vaccines (1) generate high titers of anti-hα-Syn antibodies and (2) induce robust MultiTEP-specific T-helper cell responses without activation of potentially detrimental autoreactive anti-hα-Syn T-helper cells. Generated antibodies recognize misfolded hα-Syn produced by neuroblastoma cells, hα-Syn in the brain tissues of transgenic mouse strains and in the brain tissues of dementia with Lewy body cases. Based on these results, the most promising vaccine targeting 3 B-cell epitopes of hα-Syn simultaneously (PV-1950D) has been chosen for ongoing preclinical assessment in mouse models of hα-Syn with the aim to translate it to the human clinical trials.

Published
2017

2. MultiTEP platform-based DNA vaccines for alpha-synucleinopathies: preclinical evaluation of immunogenicity and therapeutic potency

Author

Janet Petrosyan, Natalie R.S. Goldberg, Mathew Blurton-Jones, Eliezer Masliah, Anahit Ghochikyan, David H. Cribbs, Konstantin Kazarian, Irina Petrushina, Karen Zagorski, Hayk Davtyan, and Michael G. Agadjanyan

Subjects
0301 basic medicine, Aging, and promotion of well-being, Helper-Inducer, T-Lymphocytes, Cell, MultiTEP platform, T-cell mapping, Neurodegenerative, Inbred C57BL, Epitope, Transgenic, chemistry.chemical_compound, Mice, Epitopes, 0302 clinical medicine, Vaccines, DNA, 2.1 Biological and endogenous factors, Aetiology, Vaccines, Parkinson's Disease, biology, General Neuroscience, Immunogenicity, B-Lymphocyte, Neurodegenerative Diseases, T-Lymphocytes, Helper-Inducer, Anti-alpha-synuclein antibodies, medicine.anatomical_structure, 3.4 Vaccines, Neurological, alpha-Synuclein, Epitopes, B-Lymphocyte, Female, Antibody, Biotechnology, Genetically modified mouse, Clinical Sciences, Mice, Transgenic, Antibodies, Article, DNA vaccination, DNA vaccines, Vaccine Related, 03 medical and health sciences, Rare Diseases, medicine, Acquired Cognitive Impairment, Animals, Humans, Alpha-synuclein, Synucleinopathies, Neurology & Neurosurgery, B-cell mapping, Prevention, Neurosciences, DNA, Anti-α-synuclein antibodies, Prevention of disease and conditions, Brain Disorders, Mice, Inbred C57BL, 030104 developmental biology, chemistry, nervous system, Immunology, biology.protein, Immunization, Dementia, Neurology (clinical), Geriatrics and Gerontology, Therapeutic potency, 030217 neurology & neurosurgery, Developmental Biology
Abstract

We have previously demonstrated that anti-beta amyloid DNA vaccine (AV-1959D) based on our proprietary MultiTEP platform technology is extremely immunogenic in mice, rabbits, and monkeys. Importantly, MultiTEP platform enables development of vaccines targeting pathological molecules involved in various neurodegenerative disorders. Taking advantage of the universality of MultiTEP platform, we developed DNA vaccines targeting 3 B-cell epitopes (amino acids [aa]85-99, aa109-126, and aa126-140) of human alpha-synuclein (hα-Syn) separately or all 3 epitopes simultaneously. All 4 DNA vaccines (1) generate high titers of anti-hα-Syn antibodies and (2) induce robust MultiTEP-specific T-helper cell responses without activation of potentially detrimental autoreactive anti-hα-Syn T-helper cells. Generated antibodies recognize misfolded hα-Syn produced by neuroblastoma cells, hα-Syn in the brain tissues of transgenic mouse strains and in the brain tissues of dementia with Lewy body cases. Based on these results, the most promising vaccine targeting 3 B-cell epitopes of hα-Syn simultaneously (PV-1950D) has been chosen for ongoing preclinical assessment in mouse models of hα-Syn with the aim to translate it to the human clinical trials.

Published
2016

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