1. Chimeric lipoproteins for leptospirosis vaccine: immunogenicity and protective potential.
- Author
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Tapajóz RCS, Santos FDS, de Oliveira NR, Maia MAC, Seixas Neto ACP, Maiocchi LV, Souza PHFC, Oliveira TL, and Dellagostin OA
- Subjects
- Animals, Cricetinae, Epitopes, B-Lymphocyte immunology, Epitopes, B-Lymphocyte genetics, Recombinant Fusion Proteins immunology, Recombinant Fusion Proteins genetics, Adjuvants, Immunologic administration & dosage, Immunoglobulin G blood, Epitopes, T-Lymphocyte immunology, Epitopes, T-Lymphocyte genetics, Leptospira interrogans immunology, Leptospira interrogans genetics, Bacterial Outer Membrane Proteins immunology, Bacterial Outer Membrane Proteins genetics, Vaccination, Immunity, Humoral, Leptospira immunology, Leptospira genetics, Immunogenicity, Vaccine, Leptospirosis prevention & control, Leptospirosis immunology, Lipoproteins immunology, Lipoproteins genetics, Bacterial Vaccines immunology, Bacterial Vaccines genetics, Antibodies, Bacterial blood, Antibodies, Bacterial immunology
- Abstract
Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. KEY POINTS: • Several T- and B-cell epitopes were identified in all the three proteins. • Four different adjuvants were used in vaccine formulations. • Immunization stimulated significant levels of IgG2/3 in vaccinated animals., (© 2024. The Author(s).)
- Published
- 2024
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