Towards an improved SARS-CoV-2 vaccine for vulnerable population

• Autores: Míriam Echaide Górriz
• Directores de la Tesis: David Escors (dir. tes.), Grazyna Teresa Kochan (dir. tes.)
• Lectura: En la Universidad Pública de Navarra ( España ) en 2024
• Idioma: inglés
• Número de páginas: 140
• Programa de doctorado: Programa de Doctorado en Ciencias de la Salud por la Universidad Pública de Navarra
• Enlaces
  • Tesis en acceso abierto en: Academica-e
• Resumen

  • By the end of 2019, the SARS-CoV-2 emerged in Wuhan, China. It spread rapidly generating a worldwide pandemic. New and effective mRNA-based and adenovirus-based vaccines were developed to reduce virus transmission and decrease virulence of the disease (COVID- 19). All of the vaccines contained the spike (S) protein/gene/mRNA of the virus as the main antigen. Healthy and vulnerable populations were vaccinated with mRNA-based vaccines. However, the immunosenescence (accumulation of differentiated T-cells and a depletion of naïve T-cells, with inefficient TCRs for the recognition of new antigens) and inflammaging (a chronic inflammation mainly caused by the Th17 response) present in oncologic patients and elderly individuals led to the generation of an inefficient immune response against SARS-CoV-2 infection. We have analysed the immune profile of oncologic patients and healthy donors towards mRNA Pfizer/BioNtech vaccine and SARS-CoV-2 infection. We observed that both donor groups present strong immune responses against the main structural proteins of SARS-CoV- 2: spike (S), membrane (M) and nucleoprotein (N). This allowed us to identify the most immunogenic antigens of the virus. Hence, we generated a polyprotein-based vaccine containing the most immunogenic epitopes of these proteins, adjuvanted with squalene. An in vivo study in BALB/c mice showed that the polyprotein-based vaccine induced a multiepitopic cellular immune response, conferring a wider protection than the vaccine containing only the S1 subunit of the S protein. We also studied the effect of oleuropein, a bisphenol derived from olive oil plant, as a vaccine adjuvant. We analysed in vitro the effect of oleuropein in T-cells from elderly donors against the S protein of SARS-CoV-2. The results showed that oleuropein enhances the activation of S-specific T lymphocytes. An in vivo experiment was also performed, in which NSG-A2 immunosuppressed mice containing human immune cells from elderly donors were treated with oleuropein and challenged with SARS-CoV-2 delta virus. Oleuropein potentiated the immune response in some mice containing the cells from elderly donors. In conclusion, S, M and N antigens of SARS-CoV-2 can be introduced into a vaccine to generate a more complete immune response against the virus than the current vaccines on the market. In addition, further studies can be performed to investigate oleuropein as a vaccine adjuvant to enhance the immune response in both young and elderly populations.