EpiGraph Pan-coronavirus Vaccine: An Immunogenicity Study of Computationally-Predicted Antigen Vaccine in Mice

Abstract

In late 2019, a highly transmissible and pathogenic RNA virus termed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the Hubei province of China causing the coronavirus disease (COVID-19), which later on became a pandemic threatening millions of lives globally. SARS-CoV-2 is a highly variable enveloped virus consisting of a positive-sense, single-stranded RNA genome of around 30 kb. Although many vaccines have been approved in the market that have shown clinical efficacy in preventing severe respiratory diseases, the selection of accurate vaccine antigens has lagged compared to the mutation rate of RNA viruses like SARS-CoV-23. Here, we collaborated with Dr. Bette Korber, a renowned computational biologist, to utilize an algorithm called epigraph vaccine designer to design a novel pan-coronavirus vaccine, where all the antigenic peptides are generated artificially from previous SARS-CoV-2 sequencing data. The epigraph is an algorithm based on computational geometry that optimizes coverage of potential T cell epitopes within a peptide’s primary structure based on the sampled virus population, previously having shown superior efficacy in generating HIV, influenza, and pan-filovirus vaccine candidates with stronger immunogenicity compared to wild type vaccines. To investigate the viability of epigraph antigens as vaccine candidates against SARS-CoV-2 variants, we selected four SARS-CoV-2 Spike peptide sequences generated by the epigraph algorithm based on the current GISAID COVID database (cite GISAID) and cloned them into novel rhesus adenovirus vector (RhAd52) vectors to make Pan-Coronavirus Epigraph vaccines. We were curious to see the extent of epitope coverage offered by these epigraph antigens and whether epigraph antigens provide in-vivo cross-reactive immunogenicity compared to the variant vaccines. Thus, we designed an immunogenicity study utilizing the BALB/C mice, where we intramuscularly injected the epigraph cocktail vaccines along with WA1/2020, cocktail of WA1/2020 BA.4/5 (Omicron subvariants), cocktail of five historical variants including WA1/2020+B.1.351 (Beta variant first documented in South Africa in May 2020).+ B.1.617.2 (Delta variant) +BA.4/5 and (negative control. This mice immunogenicity study will also be repeated with all these antigens in using the mRNA platform. The immunogenicity analysis will mostly focus on the humoral immune responses against various SARS-CoV-2 variants of concern, pseudotyped viral neutralizing antibody titers to assess the functionality of vaccinations. We will also assess cellular immunogenicity using multicolor flow cytometry bases assays.