Evaluation of the PEΔIII-LC3-KDEL3 Chimeric Protein of Entamoeba histolytica-Lectin as a Vaccine Candidate against Amebic Liver Abscess

Abstract

Entamoeba histolytica is an intestinal parasite that causes dysentery and amebic liver abscess. E. histolytica has the capability to invade host tissue by union of virulence factor Gal/GalNAc lectin; this molecule induces an adherence-inhibitory antibody response as well as to protect against amebic liver abscess (ALA). The present work showed the effect of the immunization with PEΔIII-LC3-KDEL3 recombinant protein. In vitro, this candidate vaccine inhibited adherence of E. histolytica trophozoites to HepG2 cell monolayer, avoiding the cytolysis, and in a hamster model, we observed a vaccine-induced protection against the damage to tissue liver and the inhibition of uncontrolled inflammation. PEΔIII-LC3-KDEL3 reduced the expression of TNF-α, IL-1β, and NF-κB in all immunized groups at 4- and 7-day postinfection. The levels of IL-10, FOXP3, and IFN-γ were elevated at 7 days. The immunohistochemistry assay confirmed this result, revealing an elevated quantity of +IFN-γ cells in the liver tissue. ALA formation in hamsters immunized was minimal, and few trophozoites were identified. Hence, immunization with PEΔIII-LC3-KDEL3 herein prevented invasive amebiasis, avoided an acute proinflammatory response, and activated a protective response within a short time. Finally, this recombinant protein induced an increase of serum IgG.

Inactivated Pseudomonas PE(ΔIII) exotoxin fused to neutralizing epitopes of PEDV S proteins produces a specific immune response in mice

“…These results demonstrated that PEDV S-B group could induce Th1-dominant cellular immune responses. Our results were consistent with previous studies, which showed that PE(ΔIII) delivering antigen proteins improved cellular immune responses in vivo (Yang et al 2013;Martínez et al 2021).…”

Amebic liver abscess by Entamoeba histolytica

“…Regarding its molecular mechanism, E. histolytica uses the virulence factor Gal/GalNAc lectin in order to invade the host tissue; this molecule not only protects against ALAs but also induces an adherence-inhibitory antibody response[ 3 ]. In addition, E. histolytica has a pair of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) genes, EhLMW-PTP1 and EhLMW-PTP2 , which are expressed through cysts, cultured trophozoites, and clinical isolates[ 32 ].…”

“…Immunization using a chimeric vaccine (using the recombinant protein PEΔIII-LC3-KDEL3) was successful in preventing invasive amebiasis, avoiding acute proinflammatory response, and rapidly activating a protective response. Ultimately, this recombinant protein induced increased serum levels of IgG[ 3 ]. Additionally, in order to proactively eliminate the disease, it would be beneficial to have greater awareness among at-risk members of the public[ 8 ].…”

Entamoeba histolytica: Membrane and Non-Membrane Protein Structure, Function, Immune Response Interaction, and Vaccine Development

“…In a study conducted by Martinez-Hernandez et al (2017; 2021) [34,35], the newly developed recombinant chimeric vaccine (PE∆III-LC3-KDEL3) produced from the LC3 fragment of E. histolytica, domains I and II of Pseudomonas aeruginosa, and the carboxy-terminal signal KDEL3 in Pichia pastoris has potential as an immunogen and showed the inhibition of the adherence of trophozoites to the HepG2 cell monolayer in a hamster model. Furthermore, the vaccine protects against liver tissue damage and uncontrolled inflammation.…”