Protection against Fasciola gigantica infection in mice by vaccination with recombinant juvenile-specific cathepsin L.

Abstract

Fasciola gigantica cathepsin L1H (FgCatL1H) is one of the major cathepsin L released by juveniles of F. gigantica to aid in the invasion of host's tissues. Due to its high sequence similarity with other cathepsin L (CatL) isoforms of late stage F. gigantica, it was considered to be a good vaccine candidate that can block all CatL-mediated protease activities and affect juveniles as well as adult parasites. In this study, recombinant proFgCatL1H protein expressed in yeast, Pichia pastoris, system was mixed with Freund's adjuvants and used to subcutaneously immunize mice that were later challenged with metacercariae of F. gigantica. The percentage of worm protection in the rproFgCatL1H-vaccinated mice compared to the non-immunized and adjuvant control mice were approximately 62.7% and 66.1%, respectively. Anti-rproFgCatL1H antisera collected from vaccinated mice reacted specifically with rproFgCatL1H and other cathepsin L isoforms of F. gigantica, but the antibodies did not cross react with antigens from other trematode and nematode parasites, including Eurytrema pancreaticum, Opisthorchis viverrini, Fischoederius cobboldi, Cotylophoron cotylophorum, Gigantocotyle explanatum, Paramphistomum cervi, and Setaria labiato-papillosa. The levels of IgG1 and IgG2a in mouse sera increased significantly at two weeks after immunization and were highest during the sixth to eighth weeks after immunization. The IgG1 level was higher than IgG2a at all periods of immunization, implicating the dominance of the Th2 response. The levels of IgG1 and IgG2a in the immune sera were shown to be strongly correlated with the numbers of worm recovery, and the correlation coefficient was higher for IgG1. The levels of serum aspartate aminotransferase and alanine transaminase were significantly lower in the sera of rproFgCatL1H-vaccinated mice than in the infected control mice indicating a lower degree of liver damage. This study demonstrated a high potential of FgCatL1H vaccine, and its efficacy is currently being studied in the larger economic animals.

• Authors: Veerawat Sansri, Krai Meemon, Narin Changklungmoa, Pornanan Kueakhai, Pathanin Chantree, Pannigan Chaichanasak, Natcha Lorsuwannarat, Tadashi Itagaki, Prasert Sobhon
• Journal: Vaccine (Vaccine) Vol. 33 Issue 13 Pg. 1596-601 (Mar 24 2015) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 25701317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Helminth
• Immunoglobulin G
• Recombinant Proteins
• Vaccines, Synthetic
• Freund's Adjuvant
• Aspartate Aminotransferases
• Alanine Transaminase
• Cathepsins
• cathepsin L1, Fasciola hepatica

Topics

• Alanine Transaminase (blood)
• Animals
• Antibodies, Helminth (blood)
• Aspartate Aminotransferases (blood)
• Cathepsins (administration & dosage, genetics, immunology)
• Cross Reactions
• Enzyme-Linked Immunosorbent Assay
• Fasciola (growth & development, immunology)
• Fascioliasis (immunology, prevention & control)
• Freund's Adjuvant
• Immunoglobulin G (blood)
• Injections, Subcutaneous
• Liver (pathology)
• Metacercariae
• Mice
• Pichia (genetics)
• Recombinant Proteins (administration & dosage, immunology)
• Vaccination
• Vaccines, Synthetic (administration & dosage, immunology)