Use of Phage Display technology in development of canine visceral leishmaniasis vaccine using synthetic peptide trapped in sphingomyelin/cholesterol liposomes.

Abstract

BACKGROUND:

Leishmania parasites can cause visceral or cutaneous disease and are found in subtropical and tropical regions of the Old and New World. The pathology of the infection is determined by both host immune factors and species/strain differences of the parasite. Dogs represent the major reservoir of Leishmania infantum (syn. L. chagasi) and vaccines are considered the most cost-effective control tools for canine disease.

METHODS:

Selection of immunodominant peptides was performed by Phage Display to identify sequences recognized by L. infantum naturally infected animals. Sera from Leishmania infected animals were used in the biopanning to selection of specific peptides. Serum samples from T. cruzi infected and healthy animals were used as control. After selection, synthetic peptides were produced in membrane (spot-synthesis) in soluble form and blotting and ELISA were performed for validation of serum reactivity. Selected peptide was formulated with aluminum hydroxide and liposomes and immunization was performed in BALB/c mice. Protection was determined by qPCR after challenge infection with virulent L. infantum.

RESULTS:

We reported the selection of Peptide 5 through Phage Display technique and demonstrate its ability to promote a state of immunity against L. infantum infection in murine model after immunization using liposomes as vaccine carrier. Our results demonstrate that immunization with Peptide 5 when formulated with aluminum hydroxide and liposomes is immunogenic and elicited significant protection associated with the induction of mixed Th1/Th2 immune response against L. infantum infection.

CONCLUSION:

Peptide 5 is a promising vaccine candidate and the findings obtained in the present study encourage canine trials to confirm the effectiveness of a vaccine against CVL.

• Authors: Christina Monerat Toledo-Machado, Lilian Lacerda Bueno, Daniel Menezes-Souza, Ricardo Andrez Machado-de-Avila, Christophe Nguyen, Claude Granier, Daniella Castanheira Bartholomeu, Carlos Chávez-Olórtegui, Ricardo Toshio Fujiwara
• Journal: Parasites & vectors (Parasit Vectors) Vol. 8 Pg. 133 (Feb 28 2015) ISSN: 1756-3305 [Electronic] England
• PMID: 25889286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leishmaniasis Vaccines
• Liposomes
• Peptide Library
• Peptides
• Sphingomyelins
• Cholesterol

Topics

• Animals
• Cholesterol
• Dog Diseases (immunology, parasitology)
• Dogs
• Enzyme-Linked Immunosorbent Assay (veterinary)
• Female
• Leishmania infantum (immunology)
• Leishmaniasis Vaccines (immunology)
• Leishmaniasis, Visceral (immunology, parasitology, veterinary)
• Liposomes
• Male
• Mice
• Mice, Inbred BALB C
• Peptide Library
• Peptides (immunology)
• Sphingomyelins