Chimeric lipoproteins for leptospirosis vaccine: immunogenicity and protective potential

• Published in: Applied microbiology and biotechnology Vol. 108; no. 1; p. 424
• Main Authors: Tapajóz, Rafael Carracena de Souza, Santos, Francisco Denis Souza, de Oliveira, Natasha Rodrigues, Maia, Mara Andrade Colares, Seixas Neto, Amilton Clair Pinto, Maiocchi, Laura de Vargas, Souza, Pedro Henrique Filgueiras Coelho, Oliveira, Thaís Larré, Dellagostin, Odir Antônio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2024; Springer Nature B.V
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Aluminum; Aluminum hydroxide; Animals; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Biomedical and Life Sciences; Biotechnological Products and Process Engineering; Biotechnology; Conserved sequence; Cricetinae; E coli; Epitopes; Epitopes, B-Lymphocyte - genetics; Epitopes, B-Lymphocyte - immunology; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Hamsters; Immune response; Immune response (humoral); Immune system; Immunity, Humoral; Immunization; Immunodominance; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Immunoglobulin G - blood; Leptospira; Leptospira - genetics; Leptospira - immunology; Leptospira interrogans - genetics; Leptospira interrogans - immunology; Leptospirosis; Leptospirosis - immunology; Leptospirosis - prevention & control; Life Sciences; Lipoproteins; Lipoproteins - genetics; Lipoproteins - immunology; Lymphocytes B; Microbial Genetics and Genomics; Microbiology; Morbidity; Protein biosynthesis; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Robust control; Spirochetes; Vaccination; Vaccines; Zoonoses; Adjuvants; vaccine; Chimeric protein; Recombinant subunit vaccine; Recombinant inactivated; Recombinant bacterin; Recombinant inactivated E. coli vaccine; Leptospira
• ISSN: 0175-7598; 1432-0614; 1432-0614
• DOI: 10.1007/s00253-024-13196-1

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.