Design and Immune Profile of Multi-Epitope Synthetic Antigen Vaccine Against SARS-CoV-2: An In Silico and In Vivo Approach
Maria da Conceição Viana Invenção, Larissa Silva de Macêdo, Ingrid Andrêssa de Moura, Lucas Alexandre Barbosa de Oliveira Santos, Benigno Cristofer Flores Espinoza, Samara Sousa de Pinho, Lígia Rosa Sales Leal, Daffany Luana dos Santos, Bianca de França São Marcos, Carolina Elsztein, Georon Ferreira de Sousa, Guilherme Antonio de Souza Silva, Bárbara Rafaela da Silva Barros, Leonardo Carvalho de Oliveira Cruz, Julliano Matheus de Lima Maux, Jacinto da Costa Silva Neto, Cristiane Moutinho Lagos de Melo, Anna Jéssica Duarte Silva, Marcus Vinícius de Aragão Batista, Antônio Carlos de Freitas
Abstract
BACKGROUND: The rapid advancement of the pandemic caused by SARS-CoV-2 and its variants reinforced the importance of developing easy-to-edit vaccines with fast production, such as multi-epitope DNA vaccines. The present study aimed to construct a synthetic antigen multi-epitope SARS-CoV-2 to produce a DNA vaccine. METHODS: A database of previously predicted Spike and Nucleocapsid protein epitopes was created, and these epitopes were analyzed for immunogenicity, conservation, population coverage, and molecular docking. RESULTS: A synthetic antigen with 15 epitopes considered immunogenic, conserved even in the face of variants and that were able to anchor themselves in the appropriate HLA site, together had more than 90% worldwide coverage. A multi-epitope construct was developed with the sequences of these peptides separated from each other by linkers, cloned into the pVAX1 vector. This construct was evaluated in vivo as a DNA vaccine and elicited T CD4+ and T CD8+ cell expansion in the blood and spleen. In hematological analyses, there was an increase in lymphocytes, monocytes, and neutrophils between the two doses. Furthermore, based on histopathological analysis, the vaccines did not cause any damage to the organs analyzed. CONCLUSIONS: The present study generated a multi-epitope synthetic vaccine antigen capable of generating antibody-mediated and cellular immune responses.