Document text
Principal Investigator: Michael G Agadjanyan
Organization: INSTITUTE FOR MOLECULAR MEDICINE
Fiscal Year: 2020
Award: $389,064
Funding agency: National Institute on Aging
Project Summary
Two months after the first report of a U.S. death from COVID-19, the death rate is 228 per million people, the
tenth highest rate globally. The mortality rate from COVID-19 in those aged 45-54 years is ~5%, and it increased
to 13% in people of 50-60 years old, and sadly 80% of all U.S. coronavirus deaths occurred among people 65
years of age and older. To protect people from COVID-19, multiple groups in all over the world have begun
developing vaccines based on the genetic sequence of SARS-CoV-2. We do not know whether both cellular and
humoral immune responses are necessary for protection against the SARS-CoV-2, but recent data with
convalescent plasma administration into the COVID-19 patients indicate that vaccine inducing neutralizing
antibodies could be sufficient for the protection against this infection. More of that, it is possible that a vaccine
that contains currently unknown T cell epitopes of SARS-CoV-2 may induce in immunized subjects a cytokine
storm upon subsequent viral infection that could lead to severe adverse events, culminating in death in
particularly susceptible elderly individuals. To avoid autoreactive T cell activation, using the current AG060965
program and other NIA grants, we have developed a universal and extremely immunogenic MultiTEP vaccine
platform for A.D. vaccines targeting pathological Aβ, tau, and α-Syn. Taking advantage of this development we
propose in this Administrative Supplement to create a SARS-CoV-2 vaccine based on proprietary MultiTEP
platform technology. We hypothesize that MultiTEP platform-based vaccine could induce protective neutralizing
antibodies in immunocompromised elderly people, including MCI/AD patients. This vaccine may differ from many
others because it could stimulate adaptive immunity, providing broad coverage of human MHC polymorphisms
and activating both naive Th cells and pre-existing memory Th cells generated in response to conventional
vaccines and/or infections with various pathogens during one's lifespan without the activation of harmful virus-
specific T cells. Therefore, using our nucleic acid-based vaccine technology we will rapidly generate DNA
constructs by attaching twenty B cell epitope genes from the spike protein to MultiTEP, (ii) select several B cell
epitopes that induced virus-neutralizing antibodies in mice, (iii) generate prototype recombinant vaccine, CoV2-
2019 targeting simultaneously up to three B cell epitopes associated with production of neutralizing antibodies.
This multiepitope CoV2-2019 vaccine will be tested in aged non-human primates (model of age-associated
immunosenescence) ana transgenic mouse model of A.D./tauopathy (seasonal model of vaccination of elderly
people and MCI/AD patients previously vaccinated with tau-vaccine, AV-1980).
Terms: <(TNF)-α><2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><A β-42><A β42><A-beta 42><A-beta42><AD model><AN-1792><AN1792><Abeta-42><Abeta42><Administrative Supplement><Age><Age-Years><Alzheimer beta-Protein><Alzheimer's Amyloid beta-Protein><Alzheimer's amyloid><Alzheimer's disease model><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid beta-42><Amyloid beta-Protein><Amyloid beta42><Amyloid β><Amyloid β-42><Amyloid β-Peptide><Amyloid β-Protein><Amyloid β42><Amyloidβ-42><Amyloidβ42><Antibodies><Antibody titer measurement><Antigenic Determinants><Antisera><Antiviral Agents><Antiviral Drugs><Antivirals><Assay><Aβ><Aβ-42><Aβ42><B blood cells><B cell><B cell differentiation factor><B cell stimulating factor 2><B cells><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Epitopes><B-Cell Stimulatory Factor-2><B-Cells><B-Lymphocyte Epitopes><B-Lymphocytes><B-cell><BCDF><BSF-2><BSF2><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><Blood Plasma><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID19><COVID19 epidemic><COVID19 pandemic><CSIF><CSIF-10><Cachectin><Cell Body><Cell Culture Techniques><Cells><Cerebromeningitis><Cessation of life><CoV emergence><Coronaviridae><Coronavirus><Crab-Eating Macaque><Crab-Eating Monkey><Critical Illness><Critically Ill><Cynomolgus Monkey><Cynomolgus macaque><Cytokine Synthesis Inhibitory Factor><DNA><DNA Vaccines><Data><Death><Death Rate><Deoxyribonucleic Acid><Development><Disease Outbreaks><EBOV><Ebola virus><Elderly><Encephalomeningitis><Engineering><Epitopes><Future><Gamma interferon><Gene Proteins><Generations><Genes><Genetic><Genetic Polymorphism><Glycoproteins><Goals><Grant><Grippe><H1N1><H1N1 Virus><H5N1><H5N1 virus><HPGF><Hepatocyte-Stimulating Factor><Human><Humoral Immunities><Hybridoma Growth Factor><IFN-Gamma><IFN-beta 2><IFN-g><IFN-γ><IFNB2><IFNG><IFNγ><IL-10><IL-6><IL10><IL10A><IL6 Protein><IgG><Immune Interferon><Immune Sera><Immune response><Immunization><Immunize><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunoglobulin G><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunostimulation><Immunosuppressed Host><Individual><Infection><Influenza><Influenza A Virus, H1N1 Subtype><Influenza A Virus, H5N1 Subtype><Interferon Gamma><Interferon Type II><Interferon-gamma><Interleukin 10 Precursor><Interleukin-10><Interleukin-6><Lead><Length of Life><Longevity><Lung><Lung Respiratory System><Lymphocytopenia><Lymphopenia><M fascicularis><M. fascicularis><MERS><MERS corona virus><MERS coronavirus><MERS coronavirus disease><MERS virus><MERS-CoV><MERS-CoV disease><MGI-2><MT-bound tau><Macaca fascicularis><Macrophage-Derived TNF><Memory><Meningoencephalitis><Mice><Mice Mammals><Middle East Respiratory Syndrome><Middle East Respiratory Syndrome CoV disease><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome coronavirus disease><Middle East Respiratory Syndrome-CoV><Middle Eastern Respiratory Syndrome><Middle Eastern Respiratory Syndrome CoV disease><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome coronavirus disease><Middle Eastern Respiratory Syndrome-CoV><Modeling><Modern Man><Monkeys><Monocyte-Derived TNF><Murine><Mus><Myeloid Differentiation-Inducing Protein><NAC precursor><Naked DNA Vaccines><Nucleic Acids><Outbreaks><PARK1 protein><PARK4 protein><Pathologic><Patients><Pb element><Peptides><Plasma><Plasma Serum><Plasmacytoma Growth Factor><Play><Production><Protein Gene Products><Proteins><QS 21><QS-21 Adjuvant><QS21><Recombinant DNA Vaccines><Recombinant Vaccines><Reporting><Rest><Reticuloendothelial System, Serum, Plasma><Role><SARS Virus><SARS corona virus><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><SNCA><SNCA protein><Safety><Series><Serious Adverse Event><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Adverse Event><Severe acute respiratory syndrome coronavirus 2><Severity of illness><Splenocyte><Stimulon QS-21 Adjuvant><Suggestion><T cell response><T memory cell><T-Cell Activation><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><T8 Cells><T8 Lymphocytes><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Tauopathies><Technology><Testing><Time><Transgenic Mice><Transgenic Organisms><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Vaccinated><Vaccination><Vaccine Design><Vaccines><Viral><Viral Diseases><Viral Vaccines><Virus><Virus Diseases><Vulnerable Populations><Wuhan coronavirus><a beta peptide><a-syn><a-synuclein><abeta><adaptive immunity><advanced age><aged><ages><alpha synuclein><alphaSP22><alzheimer model><amyloid beta><amyloid-b protein><anti-viral agents><anti-viral drugs><anti-virals><antibody titering><antibody-based immunity><autoreactive T cell><avian influenza H5N1><avian influenza H5N1 virus><base><beta amyloid fibril><cell culture><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><coronavirus emergence><cytokine><cytokine release syndrome><cytokine storm><design><designing><developmental><disease severity><ebolavirus><efficacy testing><elders><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><flu infection><geriatric><heavy metal Pb><heavy metal lead><host response><immune serum><immunogenic><immunogenicity><immunopathology><immunoresponse><immunosenescence><immunosuppressed patient><influenza infection><interferon beta 2><lFN-Gamma><late life><later life><life span><lifespan><memory T lymphocyte><microtubule bound tau><microtubule-bound tau><mortality><mouse model><murine model><nCoV><neutralizing antibody><new CoV><new coronavirus><non A-beta component of AD amyloid><non A4 component of amyloid precursor><non-human primate><nonhuman primate><novel CoV><novel coronavirus><older adult><older person><pathogen><phase 1 trial><phase I trial><polymorphism><prevent><preventing><programs><prototype><pulmonary><response><senior citizen><serious adverse experience><serious adverse reaction><severe acute respiratory syndrome-CoV><social role><soluble amyloid precursor protein><tau><tau Proteins><tau associated neurodegeneration><tau associated neurodegenerative process><tau factor><tau induced neurodegeneration><tau mediated neurodegeneration><tau neurodegenerative disease><tau neuropathology><tauopathic neurodegenerative disorder><tauopathy><thymus derived lymphocyte><transgenic><vaccine evaluation><vaccine screening><vaccine testing><viral infection><virus infection><virus-induced disease><vulnerable group><α-syn><α-synuclein><τ Proteins>