Abstract Summary/Description
Severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2), which infects mainly the respiratory tract, caused a worldwide pandemic of the coronavirus disease 2019 (COVID-19) from 2020 until 2023. The emergence of new mutations is linked to consequent progressive selection of different dominate variants of concern (VOCs) (Wuhan-Hu-1 Wildtype (WT), Alpha, Delta, Omicron) and changes in viral properties. Presently, Omicron is the predominant variant, which is 2 to 4 times more transmissible and has an increased immune evasion compared to other variants. As infections continue, SARS-CoV-2 may further evolve to better evade the human immune system, such as the humoral immune system, and/or boost transmissibility. So far, existing vaccines target the highly, mutagenic spike protein (S), which allows viral entry into host epithelial cells via ACE2 receptor binding and is the main target for neutralizing antibodies (nAbs). To limit virus replication and transmission of SARS-CoV-2, a greater T-cell response is needed to eliminate virus infected cells at a more rapid rate. T-cell responses play a critical role in vaccine protection against severe COVID-19 disease by contributing to clear the infection and aiding in memory B cell activation for long-term protection. A way to increase cellular immune response is by incorporating the nucleocapsid (N) protein in vaccine development which is: 1) highly conserved amongst Sarbecovirus strains; 2) highly immunogenic; 3) abundantly expressed; and 4) interacts with various host cellular processes in the cellular immune response like inducing strong T cell responses. Thus, including a higher T cell response in the host may result in lower viral titers by eliminating virus-infected cells at a more rapid rate. The candidate vaccine will include: 1) the S protein of SARS-CoV- 2 VOC to induce the greatest nAb response to help counteract infection; 2) the N protein (highly, conserved) of SARS-CoV-2 VOC that elicits T-cell responses.
