LEAPS Technology peptide vaccines activate T cells to elicit prophylaxis and therapy for SARS-CoV-2 Ken S. Rosenthal1*, Daniel H. Zimmerman2, Hyesun Jang,3 Ying Huang,3 Ted M. Ross 3. 1Augusta University/University of Georgia Medical Partnership, Athens GA; 2 CEL-SCI Inc. Vienna VA; 3Center for Vaccines and Immunology- University of Georgia, Athens GA. Ligand Epitope Antigen Presentation System (LEAPS) peptide vaccines combine a T cell epitope containing disease related peptide with an immune cell binding ligand (ICBL) to promote immunogenicity and direct the subsequent immune response. Initial studies with peptides from the SARS-CoV-2 nucleoprotein (NP350, NP146), chosen to contain MHC-1 HLA-binding epitopes, were attached to either the J-ICBL to elicit Th1 responses or the DerG-ICBL to elicit Th2 responses. Balb/C mice immunized with either of two different types of LEAPS conjugates elicited IgG antibodies directed to the NP350 but not NP146. However, antibody to the NP protein is not expected to be protective. K18-hACE transgenic C57Bl6 mice were either unvaccinated, injected with adjuvant or vaccinated with a pool of J-NP350 and J-NP146 or a pool of DerG-NP350 and DerG-NP146 either prophylactically twice (-28 and -14 days) or therapeutically, one day post infection and then challenged with 2.2 5x10e+5 pfu/ml SARS-CoV-2 virus intranasally on study day 0. Whereas none of the control or adjuvant treated mice survived beyond day 8 post challenge, 40%-50% of mice prophylactically or therapeutically treated with LEAPS-NP vaccines survived to study end at day 12 and were regaining lost weight. The success of this therapy was statistically significant at a 95% level. These results indicate that LEAPS-peptide activated T cells directed towards the NP can deliver therapeutic protection and that the response to the vaccines is quick enough to elicit therapy from a lethal challenge with SARS-CoV-2.