EFFECTS OF CHOLINE-DERIVED IONIC LIQUIDS ON PLASMODIUM FALCIPARUM AMA1 PROTEIN AS VACCINE ADJUVANTS

Vaccine adjuvants are additives that assist in the immune response to antigens. The choices are limited by their effects on antigen stability, their affinity for antibodies, solubility, and potential toxicity. Recently, a new class of compounds, biocompatible ionic liquids (bio-IL), have been studied as vaccine adjuvants because they have great protein solvation capacity, thermal and chemical stability, and solubility in water or organic solvents. These compounds are a modern and sustainable alternative to classic vaccine adjuvants for enhancing the immunological effect of vaccines and can facilitate the logistics of their transportation and storage.¹ Using Molecular Dynamics (MD) methods, it was possible to observe solvation effects and interactions between bio-ILs derived from choline in different concentrations with the AMA1 protein from Plasmodium falciparum, the main causative agent of malaria. 5 µs simulations were performed with the hamiltonian replica exchange (HREMD) for conformational analyses and classical MD to observe the correlation times. The structure and thermodynamics of solvation were studied using minimum distance distribution functions (MDDF) and Kirkwood-Buff (KB) solvation theory. It was possible to observe that choline-derived bio-ILs increased the stability of the experimental epitope in relation to its free state in water, keeping the functional structure protected.² The main residues in disordered regions of AMA1 that were stabilized were K489, R503, K508, and R512, and the probabilities of finding the important groups of each cosolvent were described by MDDF and KB integrals. The choline cation showed complexity and variations in accumulations at different distances. These methods allowed the analysis on a molecular scale of the interactions between the protein and complex cosolvents and the effect of these interactions on their stability.