A novel multi-epitope-based universal vaccine… (R43AI174383) – Project Grant to Techimmune Inc.

Abstract: Over the last 2 years humanity has been confronting covid-19 pandemic caused by the new corona virus 2 (sars-COV-2) infection. Major gaps: mutations and deletions often occur in the genome of sars-COV-2 (predominantly in the spike protein) resulting in more transmissible and pathogenic "variants of concern" (vocs) that can escape immunity conferred by first generation covid-19 vaccines. Because most mutations and deletions that produced the 20 known vocs are concentrated on the spike protein, there is a risk that current covid-19 sub-unit vaccines based on the spike protein will fail to protect against future vocs despite inducing strong virus-specific neutralizing antibodies against the original virus strain. Among the 80 mutations/deletions present in omicron variant, 32 mutations/deletions are concentrated in the sequence spike protein alone. This emphasizes two major limitations of currently available vaccines: the need for second-generation universal coronavirus vaccines that (1) target antigens (AGS) other than the highly variable spike protein; and (2) incorporate both b- and t-cell epitopes from spike and non-spike AGS that are highly conserved in all 20 vocs and that will induce strong humoral and cell-mediated immune responses. Our long-term goal is to develop a potent second generation universal COV vaccine to stop/reduce sars-COV-2 infections and disease caused by multiple vocs. Preliminary results: we: (1) identified highly immunogenic human b and t cell target epitopes from the whole sars-COV-2 genome; (2) characterized human t cell epitopes from the whole sars-COV-2 genome that are selectively targeted by the "protective" immune system from asymptomatic covid-19 patients; and (3) produced a first prototype multi-epitope universal COV vaccine candidate using the validated mrna delivery system platform, and (4) created novel "humanized" susceptible HLA-DR/HLA-a*0201/HACE2 triple transgenic mouse model with which to test 7 additional multi-epitope universal COV vaccine candidates that bear different highly conserved human b and t cell epitopes spanning the entire COV genome. We hypothesize that one or more of our 7 universal vaccine candidates will protect "humanized" mice from infection and disease caused by intranasal inoculation with sars-COV-2 a, b, g, d and omicron vocs. Our specific aims are: aim 1: to design and construct 7 additional mrna-based universal vaccine candidates that will incorporate highly conserved b and t cell epitopes selected from 20 vocs. Aim 2: to determine the safety, immunogenicity, and protective efficacy against sars-COV-2 a, b, g, d or omicron vocs of 7 multi-epitope universal COV vaccine candidates delivered intranasally in the "humanized" HLA-DR/HLA-a*0201/HACE2 mouse model. The durability of protection and its correlation with blocking/neutralizing antibodies and the number and function of COV-specific CD4+ and CD8+ TRM cells that reside in the lungs and brains will be determined. If successful, the lead universal COV vaccine that protects against most of the 5 vocs could proceed quickly into an FDA phase 1 clinical trial

Action	Obligated	Date
Amendment	$300,000	Jan 19, 2024
Amendment	$300,000	Jan 27, 2023
Amendment	$300,000	Jan 27, 2023
Original award	$300,000	Jan 27, 2023

A novel multi-epitope-based universal vaccine against multiple coronavirus variants of concern

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