Novel pro-and eukaryotic expression plasmid expressing omicron antigens delivered via Salmonella elicited MHC class I and II based protective immunity

The latest omicron variants are emerging with mutations in the receptor binding domain (RBD) that confer immune evasion and resistance against current vaccines. Such variants have raised the peril of future vaccine effectiveness, as leading vaccines target the spike protein. Type-IV hypersensitivity, and other ailments due to the dominant Th1 response by leading vaccines, is also to be resolved. Therefore, vaccine that target diverse SARS-CoV-2 proteins and provide broad-spectrum protection and a balanced Th1 and Th2 response is an indispensable armament against the pandemic. In that prospect, a novel dual expression plasmid pJHL270 was developed and demonstrated the expression of omicron antigens exogenously from Salmonella and endogenously in the host cells. The simultaneous activation of MHC class I and II molecules culminated in a balanced Th1 and Th2 response, which was evident through the upsurge of IgG, IgA antibodies, IgG2a/IgG1 ratio, cytokine responses and CD4+, CD8+ T-lymphocytes. The level of CD44+ cells showed the trigger for Th1 and Th2 balance and memory-cell activation for long-lasting immunity. The level of IFN-gamma + cells and neutralizing antibodies signifies the anti-viral response. The vaccine protected the hamsters from BA.5 and BA.2.75 omicron viral-challenge, exhibited a significant reduction in lung viral-load and histopathological lesions. In addition to two-way anti-gen expression and bilateral immune elicitation, this Salmonella-based vaccine delivery system can be prospec-tively applied to humans and a broad range of animals as a convenient alternative to viral and chemical vaccine delivery approaches.

Automated summary

The latest omicron variants have mutations in the RBD that result in immune evasion and resistance to current vaccines. These variants pose a threat to vaccine effectiveness as most vaccines target the spike protein. Additionally, the dominant Th1 response induced by current vaccines needs to be addressed. Therefore, a vaccine that targets multiple SARS-CoV-2 proteins and provides broad-spectrum protection, as well as a balanced Th1 and Th2 response, is crucial in combating the pandemic.