Repurposing of Universal and Immunogenic MultiTEP Platform Designed for AD to Develop SARS-CoV-2 Multiepitope Vaccine

  • Funded by National Institutes of Health (NIH)
  • Total publications:0 publications

Grant number: unknown

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2019
    2022
  • Known Financial Commitments (USD)

    $389,064
  • Funder

    National Institutes of Health (NIH)
  • Principle Investigator

    Pending
  • Research Location

    United States of America, Americas
  • Lead Research Institution

    INSTITUTE FOR MOLECULAR MEDICINE
  • Research Category

    Vaccines research, development and implementation

  • Research Subcategory

    Pre-clinical studies

  • Special Interest Tags

    Gender

  • Study Subject

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

Project SummaryTwo months after the first report of a U.S. death from COVID-19, the death rate is 228 per million people, thetenth highest rate globally. The mortality rate from COVID-19 in those aged 45-54 years is ~5%, and it increasedto 13% in people of 50-60 years old, and sadly 80% of all U.S. coronavirus deaths occurred among people 65years of age and older. To protect people from COVID-19, multiple groups in all over the world have begundeveloping vaccines based on the genetic sequence of SARS-CoV-2. We do not know whether both cellular andhumoral immune responses are necessary for protection against the SARS-CoV-2, but recent data withconvalescent plasma administration into the COVID-19 patients indicate that vaccine inducing neutralizingantibodies could be sufficient for the protection against this infection. More of that, it is possible that a vaccinethat contains currently unknown T cell epitopes of SARS-CoV-2 may induce in immunized subjects a cytokinestorm upon subsequent viral infection that could lead to severe adverse events, culminating in death inparticularly susceptible elderly individuals. To avoid autoreactive T cell activation, using the current AG060965program and other NIA grants, we have developed a universal and extremely immunogenic MultiTEP vaccineplatform for A.D. vaccines targeting pathological Aβ, tau, and α-Syn. Taking advantage of this development wepropose in this Administrative Supplement to create a SARS-CoV-2 vaccine based on proprietary MultiTEPplatform technology. We hypothesize that MultiTEP platform-based vaccine could induce protective neutralizingantibodies in immunocompromised elderly people, including MCI/AD patients. This vaccine may differ from manyothers because it could stimulate adaptive immunity, providing broad coverage of human MHC polymorphismsand activating both naive Th cells and pre-existing memory Th cells generated in response to conventionalvaccines 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 DNAconstructs by attaching twenty B cell epitope genes from the spike protein to MultiTEP, (ii) select several B cellepitopes 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-associatedimmunosenescence) ana transgenic mouse model of A.D./tauopathy (seasonal model of vaccination of elderlypeople and MCI/AD patients previously vaccinated with tau-vaccine, AV-1980).