Ysrafil Ysrafil
1* 
, Zulfiayu Sapiun
2,3 , Indwiani Astuti
4 , Mohammad Anas Anasiru
5, Nangsih Sulastri Slamet
2 , Hartati Hartati
2 , Fadli Husain
2, Sukmawati Ahmad Damiti
6 1 Faculty of Medicine, Universitas Palangka Raya, Palangka Raya 73111, Indonesia
2 Department of Pharmacy, Health Polytechnic of Gorontalo, Gorontalo 96135, Indonesia
3 Department of Pharmacy, Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia
4 Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
5 Department of Nutrition, Health Polytechnic of Gorontalo, Gorontalo 96135, Indonesia
6 Department of Midwifery, Health Polytechnic of Palangka Raya, Palangka Raya 73111, Indonesia
Abstract
Introduction: The current incidence of the novel coronavirus disease has shown only small reductions of cases and has become a major public health challenge. Development of effective vaccines against the virus is still being encouraged such as multi-epitope vaccines designed from the components of SARS-CoV-2 including its spike, nucleocapsid and ORF1a proteins. Since the addition of adjuvants including HABA protein and L7/L12 ribosomal are considered helpful to increase the effectiveness of the designed vaccine, we proposed to design multiepitope vaccines by two different adjuvants.
Methods: We used the IEDB server to predict BCL and TCL epitopes that were characterized using online tools including VaxiJen, AllPred and IL-10 Prediction. The selected epitopes were further constructed into multiepitope vaccines. We also added two different adjuvants to the vaccine components in order to increase the effectiveness of the vaccines. The 3D-structured vaccines were built using trRosetta. They were further docked with different Toll-like-receptors (TLR 3, 4 and 8) and the entry receptor of SARS-CoV-2, ACE2 using ClusPro, PatchDock and refined by FireDock. All structures were visualized by USCF Chimera and PyMOL.
Results: In this study, we succeeded in designing two different candidate vaccines by the addition of HABA protein and L7/L12 ribosomal as adjuvants. The two vaccines were almost equally good in terms of their physicochemical properties and characteristics. Likewise, their strong interactions with TLR3 4, 8 and ACE2 show the lowest energy level of both was estimated at more than -1,000. Interactions of vaccines with ACE2 and TLRs are essential for activation of immune responses and production of antibodies.
Conclusion: The two designed and constructed multiepitope vaccine have good characteristics and may have the potential to activate humoral and cellular immune responses against SARS-CoV-2. Further research is worth considering to confirm the findings of this study.