(M1530-01-01) A Promising Peptide-Based Universal Vaccine against MERS-CoV and SARS-CoV2 Coronaviruses

Purpose: Coronaviruses are enveloped viruses with an RNA genome inside a nucleocapsid. There are more than 15 known coronaviruses that exist across species such as bats and camel. The recent deadly outbreaks of SARS-CoV in 2003, MERS-CoV in 2012, and the SARS-CoV2 (COVID-19) outbreak have accelerated the development of treatments and vaccines by the government and private sectors. However, there is still a need for an economically viable universal vaccine against coronaviruses in animals and humans. This study aims to develop a safe and effective peptide-based novel microspheres formulation as a promising universal vaccine against MERS-CoV and SARS-CoV2 viruses.

Methods: A newly formulated microsphere containing SARS-Cov2 and MERS peptides (D-Pep-MPs) was made from a composition of biodegradable polymers and lipids. Another polymeric-based Microsphere formulation loaded with peptides (P-Pep-MPs) was made as a control. A modified double emulsion method was used to maximize the encapsulation efficiency of the hydrophilic and hydrophobic peptides mixture inside the microspheres. The D-Pep-MPs and P-Pep-MPs were characterized using a scanning electron microscope (SEM). A mouse and human peripheral blood mononuclear cells (PBMCs) were extracted from mice and human subjects vaccinated for SARS-Cov2 and MERS coronaviruses. PBMCs were used to evaluate D-Pep-MPs and P-Pep-MPs performance in vitro.

Results: D-Pep-MPs and P-Pep-MPs were 3-30 µm in size, with a spherical shape. D-Pep-MPs rougher surfaces and more irregular edges than P-Pep-MPs. PBMCs from vaccinated mice were treated with D-Pep-MPs, P-Pep-MPs, and a mixture of the free peptides. D-Pep-MPs treated cells showed significantly higher INF-gamma/CD4 (2.5 fold increase), INF-gamma/CD8 (2 fold increase), and overall total INF-gamma response (2 fold increase) than P-Pep-MPs treated cells. As expected, D-Pep-MPs showed significantly higher INF-gamma/CD4 (2.5 fold increase) and INF-gamma/CD8 (2.5 fold increase) responses when compared to the free peptides group. Similarly, human-treated PBMCs showed the highest increase of INF-gamma/CD8 levels in cells treated with D-Pep-MPs, followed by P-Pep-MPs and then free peptides. More importantly, D-Empty-MPs showed a significantly higher INF-gamma/CD4, INF-gamma/CD8, and overall total INF-gamma response, when compared to P-Empty-MPs, treated cells. This indicates that our novel D-MPs have some adjuvant-like activities when compared to other polymeric microspheres.

Conclusion: We prepared and characterized a novel D-Pep-MPs formulation that has favorable in vitro characteristics for peptide-based vaccine delivery. The D-MPs showed strong adjuvant-like activities in both mice and human PBMCs.

Acknowledgements:This work was supported by King Abdullah International Medical Research Center (KAIMRC), research contract/grant number RCR798 (RC18/272/R), and research grant number RC20/183/R COVID-19.

SEM images of novel D-Pep-MPs formulation