Differential protective impact of peptide vaccine formulae targeting the lung- and liver-stage of challenge Schistosoma mansoni infection in mice

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Tallima H.; Tadros M.M.; El Ridi R.

Journal: Acta Tropica

Publisher: Elsevier B.V.

Publication Date: June 2024

Volume / Issue: Volume 254

Article No.: 107208

ISSN: 0001706X

DOI: 10.1016/j.actatropica.2024.107208

Scopus: View on Scopus

PubMed: 38621620

Document Type: Article

Authors and Affiliations

Tallima H., Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt, Department of Chemistry, School of Sciences and Engineering, American University in Cairo, Cairo, New Cairo, 11835, Egypt; Tadros M.M., Department of Parasitology, Theodore Bilharz Research Institute, Warrak El-Hadar, Giza, Imbaba, 12411, Egypt; El Ridi R., Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt

Abstract

The study aimed to elicit protective immune responses against murine schistosomiasis mansoni at the parasite lung- and liver stage. Two peptides showing amino acid sequence similarity to gut cysteine peptidases, which induce strong memory immune effectors in the liver, were combined with a peptide based on S. mansoni thioredoxin peroxidase (TPX), a prominent lung-stage schistosomula excretory-secretory product, and alum as adjuvant. Only one of the 2 cysteine peptidases-based peptides in a multiple antigenic peptide construct (MAP-3 and MAP-4) appeared to adjuvant protective immune responses induced by the TPX peptide in a MAP form. Production of TPX MAP-specific IgG1 serum antibodies, and increase in lung interleukin-1 (IL-1), uric acid, and reactive oxygen species (ROS) content were associated with significant (P < 0.05) 50 % reduction in recovery of lung-stage larvae. Increase in lung triglycerides and cholesterol levels appeared to provide the surviving worms with nutrients necessary for a stout double lipid bilayer barrier at the parasite-host interface. Surviving worms-released products elicited memory responses to the MAP-3 immunogen, including production of specific IgG1 antibodies and increase in liver IL-33 and ROS. Reduction in challenge worm burden recorded 45 days post infection did not exceed 48 % associated with no differences in parasite egg counts in the host liver and small intestine compared to unimmunized adjuvant control mice. Alum adjuvant assisted the second peptide, MAP-4, in production of IgG1, IgG2a, IgG2b and IgA specific antibodies and increase in liver ROS, but with no protective potential, raising doubt about the necessity of adjuvant addition. Accordingly, different vaccine formulas containing TPX MAP and 1, 2 or 3 cysteine peptidases-derived peptides with or without alum were used to immunize parallel groups of mice. Compared to unimmunized control mice, significant (P < 0.05 to < 0.005) 22 to 54 % reduction in worm burden was recorded in the different groups associated with insignificant changes in parasite egg output. The results together indicated that a schistosomiasis vaccine able to entirely prevent disease and halt its transmission still remains elusive. © 2024 Elsevier B.V.

Keywords

Gut cysteine proteases, multiple antigenic peptides, cytokines, reactive oxygen species; Schistosoma mansoni, schistosomiasis vaccine; Adjuvants, Immunologic; Alum Compounds; Animals; Antibodies, Helminth; Antigens, Helminth; Disease Models, Animal; Female; Immunoglobulin G; Liver; Lung; Mice; Mice, Inbred BALB C; Protein Subunit Vaccines; Schistosoma mansoni; Schistosomiasis mansoni; Vaccines, Subunit; aluminum potassium sulfate; cholesterol; cysteine proteinase; cytokine; immunoglobulin A antibody; immunoglobulin G1 antibody; immunoglobulin G2a; immunoglobulin G2b; interleukin 1; interleukin 33; lipid; multiple antigenic peptide; multiple antigenic peptide 3; multiple antigenic peptide 4; peptide vaccine; reactive oxygen metabolite; synthetic peptide; thioredoxin peroxidase; triacylglycerol; unclassified drug; uric acid; aluminum sulfate; helminth antibody; immunological adjuvant; parasite antigen; subunit vaccine; amino acid; immune response; peptide; reactive oxygen species; rodent; schistosomiasis; vaccine; adult; amino acid sequence; animal experiment; animal model; animal tissue; antibody blood level; antibody response; Article; cholesterol level; controlled study; cytokine response; immunological memory; larva; lipid bilayer; male; mouse; nonhuman; parasite egg count; parasitological parameters; schistosomulum; sequence homology; small intestine; triacylglycerol level; worm burden; animal; Bagg albino mouse; blood; disease model; immunology; parasitology

Citation Information

Scopus Citations: 2

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