PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: a review of literature

Antoine Fakhry AbdelMassih, Rahma Menshawey, Jumana H. Ismail, Reem J. Husseiny, Yousef M. Husseiny, Shenoda Yacoub, Aya Kamel, Rafeef Hozaien, Elaria Yacoub, Esraa Menshawey, Abanoub Abdelmalek, Ahmed Abouelazaem, Ahmed Elhatw, Ahmed Aboelmaaty, Alaaelrahman Shahib, Amany Mansour, Aya Kamal, Basant Mohamed, Bemen Atif, Beshoy Ghabreal, Catherine Abdelmalak, David Ibrahim, Ebtesam Elsaify, Farah Magdy, Farid G. Hanna, Hadeer Hafez, Hafsa Dahir, Kerlos Merhom, Maram Ahmed, Mariam Bishara, Mina Tawfik, Mina Youssef, Mohamed El Sharnouby, Mourad Hamouda, Musheera Ammar, Nada Ali, Nada Daniel, Nadine El-Husseiny, Noha Abdelraouf, Nuran K. Abdelhameed, Radwa Ahmed, Radwa Othman, Rahma Mohamadein, Rana Allam, Rana Elgendy, Rana Shebl, Saged Elsherbiney, Sarah Fouad, Sara Emel, Sara Owais, Sarah Hetta, Samah El-Saman, Shaimaa Abdelalim, Sherin Galal, Yara Asar, Yara Osman, Yasmeen Khalaf, Youstina Aziz, Yousra Khafagy, Nervana Gamal, Biagio Castaldi

Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.