Pan Coronavirus Vaccine
The three major problems of the current COVID-19 vaccines in the U.S. include 1) the adverse epitopes on full-length SARS-CoV-2 (SCoV2) spike glycoprotein for vaccine immunogen, 2) the inflammatory nature of the lipid nanoparticle (LNP) used as mRNA-LNP delivery, and 3) failure to prevent SCoV2 infection like other COVID-19 vaccines. The most well-described adverse epitopes on the SCoV2 spike are the inflammatory superantigen, intercellular adhesion molecule 1, bullous pemphigoid, and neurotoxin motifs. Our multivalent B-cell constructs (RBD-HR1-SH-HR2-TM-CT) are devoid of such adverse epitopes and were carefully designed using I-TASSER homology modeling. These B-cell constructs retain the receptor binding domain (RBD) for major neutralizing antibody (NAb) epitopes against SCoV2 variants and stem helix (SH) as broadly NAb epitopes against ß-coronaviruses. The SCoV2 spike has a few conserved cytotoxic T lymphocyte (CTL) epitopes constantly mutating. Consequently, CTL and T-helper (TH) epitopes were identified on the least mutating, SCoV2s' and aCoVs' RdRp polymerases and M-proteases using CTL/DRB algorithms. The CTL/TH epitope chains in pDNA/mRNA were integrated with B-cell constructs into an improved LNP, which targets the spleen. The minimalistic pan-CoV vaccine for cats was derived from SCoV2 Wuhan, feline coronavirus serotype 1, and FCoV2 B-cell constructs and T-cell/CTL epitope chains of pDNA/mRNA in the improved LNP delivery system (PCT/US23/72907). Remarkable serological and T-cell cross-reactivities reside on SCoV2, human aCoV, and FCoV1 RBDs. The pilot feline pan-CoV vaccine has been safely vaccinated at a high dose, equivalent to a high adult human dose (50 µg), intramuscularly in laboratory cats (3.0-3.1 kg) with no adverse reactions. Initial results show enhanced T-cell responses to FCoV1 RBD upon first feline pan-CoV vaccination. This feline vaccine also serves as a proof of concept model for the human pan-CoV vaccine. The minimalistic pan-CoV vaccine for humans consists of B-cell constructs and CTL/TH epitope chains in pDNA/mRNA of SCoV2 Wuhan, SCoV2 variant, and two human aCoVs in an LNP delivery system (U.S. Patent Application 63/508,697). Most importantly, combining the B-cell and T-cell epitopes in the pan-CoV vaccine, such bimodal immune mechanisms should generate potent sterilizing immunity to prevent SCoV2 infection in humans and cats, with minimal to no adverse effects.