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

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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).