LemA and Erp Y-like recombinant proteins from Leptospira interrogans protect hamsters from challenge using AddaVax™ as adjuvant

• Published in: Vaccine 2018-05, Vol.36 (19), p.2574-2580
• Main Authors: Oliveira, Thaís Larré, Schuch, Rodrigo Andrade, Inda, Guilherme Roig, Roloff, Bárbara Couto, Neto, Amilton Clair Pinto Seixas, Amaral, Marta, Dellagostin, Odir Antonio, Hartwig, Daiane Drawanz
• Format: Article
• Language: English
• Subjects: AddaVax; Adhesins; Adjuvant; Adjuvants; Adjuvants, Immunologic - pharmacology; Animals; Antigens; Bacterial Proteins - genetics; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Bacterial Vaccines - pharmacology; Collagen (type IV); Control methods; Cricetinae; E coli; Enzyme-linked immunosorbent assay; Enzymes; Erp Y-like; Experiments; Extracellular matrix; Female; Fibrinogen; Formulations; Gangrene; Genomes; Hamsters; Histopathology; Immune response; Immune response (humoral); Immune system; Immunization; Immunogenicity; Immunoglobulin G; Kidneys; Laminin; LemA; Leptospira; Leptospira interrogans; Leptospira interrogans - genetics; Leptospira interrogans - pathogenicity; Leptospirosis; Leptospirosis - immunology; Leptospirosis - prevention & control; Lesions; Lungs; Male; Mice, Inbred BALB C; Pathogenesis; Polysorbates - pharmacology; Proteins; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Squalene; Squalene - pharmacology; Transcription Factors - genetics; Vaccine; Vaccine efficacy; Vaccines; Vaccines, Synthetic - immunology; Vaccines, Synthetic - pharmacology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.03.078

Recombinant subunit vaccines have been extensively evaluated as promising alternatives against leptospirosis. Here, we evaluated two proteins in formulations containing the adjuvant AddaVax™ as vaccine candidates for prevention and control of leptospirosis. Recombinant proteins rErp Y-like and rLemA were characterized by ELISA to assess their ability to bind extracellular matrix (ECM) components and fibrinogen. Groups of eight hamsters were immunized intramuscularly with rErp Y-like or rLemA mixed with a squalene-based adjuvant (AddaVax), and then vaccine efficacy was determined in terms of protection against a lethal challenge. The humoral immune response was determined by ELISA, and the evidence of sub-lethal infection was evaluated by histopathology and kidney culture. rLemA protein binds laminin, fibrinogen, and collagen type IV, while rErp Y-like interacts with fibrinogen. Significant protection was achieved for rLemA and rErp Y-like vaccines, which showed 87.5% and 62.5% survivals, respectively. On day 28, the humoral immune response was significantly greater in the vaccine groups as compared to that in the control group, and the response was predominantly based on IgG2/3. The surviving animals showed negative results in culture isolation but presented with tissue lesions in the lungs and kidneys. Cumulatively, our findings suggest that LemA and Erp Y-like proteins act as adhesins and are able to protect against mortality, but not against tissue lesions. Moreover, AddaVax is a novel adjuvant with potential for improving the immunogenicity of leptospiral vaccines.