A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach

Abstract

Malaria is a complex disease caused by parasites of the genus Plasmodium and is the leading cause of morbidity and mortality worldwide. The most severe form of malaria disease is caused by Plasmodium falciparum. Thus, a combination of different approaches is needed to control malaria. Resistance to first-line drugs and insecticides, on the other hand, makes the need for an effective vaccination more urgent than ever. Because erythrocyte parasites cause the most clinical symptoms, developing a vaccination for this stage of infection might be highly beneficial. In this research, we employed various bioinformatics methods to create an efficient multi-epitope vaccine that induces antibodies against the blood stage of malaria infection. For this purpose, we selected the malaria PfGARP protein as the target here. The B, HTL epitopes, and epitope conservation were predicted. The predicted epitopes (including 5 B and 5 HTL epitopes) were connected using suitable linkers, and the flagellin molecule was used as an adjuvant to improve its immunogenicity. The final construct vaccine with 414 amino acids long was designed. The vaccine's allergenicity, antigenicity, solubility, physicochemical characteristics, 2D and 3D structure modeling, molecular docking, molecular dynamics simulation, in silico cloning, and immunological simulation were tested. In silico immune simulation results showed significantly elevated IgG1 and IgM and T helper cells, INF γ, IL 2, and B-cell populations after the injection of the designed vaccine. These significant computational analyses indicated that our proposed vaccine candidate might activate suitable immune responses against malaria. However, in vitro and in vivo studies are essential for further validation.

In silico design and immunoinformatics analysis of a universal multi-epitope vaccine against monkeypox virus

“…In this study, like many other studies, the AAY linker was used to connect CTL epitopes [ 85 , 111 , 112 ], the GGGGS linker to connect HTL epitopes [ 113 , 114 ], the KK linker to connect LBL epitopes [ 115 – 117 ], and the EAAAK linker to connect adjuvant [ 116 , 118 , 119 ]. The AAY linkers help to increase epitope presentation while decreasing the formation of junctional epitopes [ 120 ]. The GGGGS linker, which is made up of small or polar amino acids like Gly and Ser, provides good flexibility and solubility and is an excellent choice for fusion protein domains that require specific movements or interactions [ 121 ].…”

“…The KK linker is a target for cathepsin B, a key protease in antigen processing. This linker helps in the reduction of junctional immunogenicity by preventing antibody induction for the peptide sequence formed when the individual epitopes are linearly connected [ 120 ]. The EAAAK linker is a rigid alpha-helix-forming peptide linker that functions as a domain spacer in fusion proteins [ 122 ].…”

Protective Efficacy of Multiple Epitope-Based Vaccine against Hyalomma anatolicum, Vector of Theileria annulata and Crimean–Congo Hemorrhagic Fever Virus

“…Both structures fluctuated, indicating their considerable flexibility and validating it as suitable vaccine structures. Similarly, Atapour et al [58] recorded a high degree of fluctuation in the residues at positions 219 and 617 in a P. falciparum multi-epitope vaccine. The results obtained in the form of B-factor and deformability plots indicated that the molecular structures of both of the peptides were stable, and the overall stability of the VT2 constructs was higher compared to the VT1.…”

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

“…A multi-epitope vaccine was designed against the blood stage of P. falciparum by selecting multiple epitopes of P. falciparum glutamic acid-rich protein (PfGARP) protein. A total of 10 epitopes (5 B and 5 HTL epitopes) were linked by suitable linkers along with flagellin adjuvant to enhance the immunogenicity of the vaccine construct (169). While in silico immune simulation resulted in an elevated humoral and cellular immune response against malaria, such in silico studies need further in vitro and in vivo evaluations (169).…”

“…A multi-epitope vaccine was designed against the blood stage of P. falciparum by selecting multiple epitopes of P. falciparum glutamic acid-rich protein ( Pf GARP) protein. A total of 10 epitopes (5 B and 5 HTL epitopes) were linked by suitable linkers along with flagellin adjuvant to enhance the immunogenicity of the vaccine construct ( 169 ). While in silico immune simulation resulted in an elevated humoral and cellular immune response against malaria, such in silico studies need further in vitro and in vivo evaluations ( 169 ).…”