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Principal Investigator: Hawa Vahed
Organization: TECHIMMUNE, LLC
Fiscal Year: 2024
Award: $300,000
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY
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
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