In Silico Analysis: The Effect of Adjuvant on Multi-epitope Vaccine SARS-COV-2 against Toll like Receptor 4 (TLR4) Signaling M. Afrizal Firmansyah(a), Aris Susilo(a), Dian Marlina(a), Andri Prasetiyo(b), Rina Herowati (a*)
a) Faculty of Pharmacy, Universitas Setia Budi, Jl. Letjend Sutoyo, 57127 Surakarta, Indonesia
* rinaherowati[at]setiabudi.ac.id
b) Faculty of Pharmacy, Universitas Pancasila, Jl. Lenteng Agung Raya No.56, 12640 Jakarta, Indonesia
Abstract
Booster doses of the SARS CoV 2 vaccine that have been developed are still needed since the neutralization effect of vaccines decreases. Developing of vaccines with the addition of adjuvants using the subunit method is considered necessary in order to activate the innate immune system and trigger an adaptive immune response. Aluminum Hidroxide (AlOH) based adjuvants, the first vaccine adjuvant, have been used popularly in most human vaccines. However, they lack ability to intervene in cell-mediated immunity such as Toll-Like Receptors. This study aims to predict the effect of adjuvants in the SARS CoV 2 multi-epitope vaccine on Toll-Like Receptor 4 signaling using in silico analysis. Webserver-based designed vaccine was created using sequences from Uniprot. The highest antigenicity sequence was identified in this study. Epitope MHC I, II, and B Cells. NetCTL 1.2 were used to predict MHC I epitope. IEDB was used to predict MHC II epitope and B cells. The epitope was constructed in 3D with TrRosetta by combining the obtained epitope with adjuvant Ribosomal 50S L7/L12 (rpIL) and Beta Defensin (hBDs). Molecular anchoring was carried out using HADDOCK 2.4. Molecular dynamics simulation was generated by YASARA. The obtained rpIL and hBDs design vaccines were structurally stable, nontoxic, and nonallergenic. hBDs vaccine design showed the highest antigenicity compared to rpIL with antigenicity of 0.5134 and 0.5114. The molecular docking of the hBDs design had a high predicted binding of -119.55 Kcal/mol, while rpIL had a predicted binding of -89.83 Kcal/mol. Molecular dynamics predictions in the two vaccine designs showed similar results, vaccine designs with hBDs adjuvant possed stronger TLR4 signaling than rpIL adjuvant. The average RMSD and RMSF of the hBDs design were 5.224 Angstrom and 2.05 Angstrom. On the other hand, the Ribosomal 50S L7/L12 adjuvant had the average RMSD and RMSF of 5.12 Angstrom and 2.01 Angstrom.
