Chimeric lipoproteins for leptospirosis vaccine: immunogenicity and protective potential

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...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0175-7598 1432-0614 1432-0614
DOI:	10.1007/s00253-024-13196-1