Evaluation of the vaccine potential of antigenic fractions obtained in Leptospira interrogans serovar Copenhageni using hamsters as an animal model

• Grant number: 16/11541-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2016
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Aline Florencio Teixeira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/17488-2 - Advancing the understanding of pathogenesis and virulence of Leptospira interrogans through proteomics, structural, mutagenesis and immunological analyses, AP.TEM
• Associated scholarship(s): 19/05466-4 - Identification of leptospiral antigens recognized by gamma/delta T cells as target for development of next generation vaccines, BE.EP.PD

Abstract

Leptospirosis, considered an important worldwide zoonosis represents a serious public health problem. Caused by pathogenic bacteria of the genus Leptospira, the number of infections in the world can reach one million per year. In Brazil, outbreaks occur mainly during rainy periods in metropolitan areas that have inadequate infrastructure, such a condition favors the proliferation of rodents that are considered the main reservoirs of the disease. The prevention of leptospirosis by vaccination is an alternative to control the spread of the disease. However, the vaccines available for leptospirosis are based on inactivated bacteria and immune protection is dependent on the production of antibodies against the specific lipopolysaccharides of each serovar. As a consequence, a classic T cell response is not activated and results in the need for an annual boost. The search for vaccine candidates that promote the activation of an immune memory response will contribute to the development of new vaccine strategies for the control of leptospirosis. Protein fractions obtained from cultured leptospires have been investigated recently, and demonstrated the ability to activate populations of CD4 T cells and ³´ T cells after stimulation of peripheral blood mononuclear cells from immunized cattle, suggesting the ability of these fractions to activate memory populations. As the use of a single major leptospira protein was not able to promote such a response, we believe that perhaps a set of proteins is necessary to promote this activation. Thus, clarifying whether animals immunized with these protein fractions would be able to activate the same profile of response and whether this response would result in protection after a challenge trial will be extremely important for the discovery of new vaccine targets and in the understanding of the protective immune responses involved in the control of leptospirosis.

Scientific publications

(11)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NASCIMENTO FILHO, EDSON G.; VIEIRA, MONICA L.; TEIXEIR, ALINE F.; SANTOS, JADEMILSON C.; FERNANDES, LUIS G. V.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; ROSSINI, AMANDA; KOCHI, LEANDRO T.; CAVENAGUE, MARIA F.; et al. Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications. JOURNAL OF PROTEOMICS, v. 180, n. SI, p. 80-87, MAY 30 2018. (17/01411-5, 17/06731-8, 14/50981-0, 17/01102-2, 16/11541-0, 16/04295-3, 16/01384-5)

TEIXEIRA, ALINE F.; FERNANDES, LUIS G. V.; SOUZA FILHO, ANTONIO; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O.. Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis. BIOMED RESEARCH INTERNATIONAL, 2018. (16/11541-0, 14/50981-0, 17/06731-8)

TEIXEIRA, ALINE F.; FERNANDES, V, LUIS G.; CAVENAGUE, MARIA F.; TAKAHASHI, MARIA B.; SANTOS, JADEMILSON C.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; KOCHI, LEANDRO T.; VIEIRA, MONICA L.; NASCIMENTO, ANA L. T. O.. Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines. Vaccine, v. 37, n. 30, p. 3961-3973, JUL 9 2019. (17/01411-5, 17/06731-8, 17/25167-6, 14/50981-0, 17/01102-2, 16/11541-0, 17/26223-7, 17/00236-5, 16/01384-5)

DAROZ, BRENDA BEVILAQUA; VIRGILIO FERNANDES, LUIS GUILHERME; TEIXEIRA, ALINE FLORENCIO; TABET OLLER NASCIMENTO, ANA LUCIA. In Silico Structural and Functional Characterization of HtrA Proteins of Leptospira spp.: Possible Implications in Pathogenesis. TROPICAL MEDICINE AND INFECTIOUS DISEASE, v. 5, n. 4, DEC 2020. (18/21959-8, 17/06731-8, 16/11541-0, 14/50981-0)

CAVENAGUE, MARIA F. F.; TEIXEIRA, ALINE F. F.; FERNANDES, LUIS G. V.; NASCIMENTO, ANA L. T. O.. LIC12254 Is a Leptospiral Protein That Interacts with Integrins via the RGD Motif. TROPICAL MEDICINE AND INFECTIOUS DISEASE, v. 8, n. 5, p. 15-pg., 2023-04-26. (18/08131-0, 19/17488-2, 16/11541-0, 17/06731-8)

TAKAHASHI, MARIA BEATRIZ; TEIXEIRA, ALINE FLORENCIO; NASCIMENTO, ANA LUCIA TABET OLLER. Overcoming problems to produce the recombinant protein LipL21 of Leptospira interrogans. BIOTECHNIQUES, v. N/A, p. 6-pg., 2023-04-17. (14/50981-0, 19/17488-2, 17/26223-7, 16/11541-0)

TEIXEIRA, ALINE F.; FERNANDES, LUIS G. V.; SOUZA FILHO, ANTONIO; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O.. Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis. BIOMED RESEARCH INTERNATIONAL, v. 2018, p. 13-pg., 2018-01-01. (14/50981-0, 16/11541-0, 17/06731-8)

NASCIMENTO FILHO, EDSON G.; VIEIRA, MONICA L.; TEIXEIR, ALINE F.; SANTOS, JADEMILSON C.; FERNANDES, LUIS G. V.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; ROSSINI, AMANDA; KOCHI, LEANDRO T.; CAVENAGUE, MARIA F.; et al. Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications. JOURNAL OF PROTEOMICS, v. 180, p. 8-pg., 2018-05-30. (14/50981-0, 17/01411-5, 17/01102-2, 16/01384-5, 16/04295-3, 16/11541-0, 17/06731-8)

TEIXEIRA, ALINE F.; CAVENAGUE, MARIA F.; KOCHI, LEANDRO T.; FERNANDES, LUIS G.; SOUZA, GISELE O.; DE SOUZA FILHO, ANTONIO FRANCISCO; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS BRYAN; NASCIMENTO, ANA L. T. O.. Immunoprotective Activity Induced by Leptospiral Outer Membrane Proteins in Hamster Model of Acute Leptospirosis. FRONTIERS IN IMMUNOLOGY, v. 11, OCT 30 2020. (14/50981-0, 17/06731-8, 18/09652-4, 18/08131-0, 16/11541-0)

CAVENAGUE, MARIA F.; TEIXEIRA, ALINE F.; FILHO, ANTONIO S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O.. Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen, vitronectin and complement binding properties. INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, v. 309, n. 2, p. 116-129, MAR 2019. (16/11541-0, 14/50981-0, 16/04295-3)

DAROZ, BRENDA B.; FERNANDES, LUIS G. V.; CAVENAGUE, MARIA F.; KOCHI, LEANDRO T.; PASSALIA, FELIPE J.; TAKAHASHI, MARIA B.; NASCIMENTO FILHO, EDSON G.; TEIXEIRA, ALINE F.; NASCIMENTO, ANA L. T. O.. A Review on Host-Leptospira Interactions: What We Know and Future Expectations. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, p. 13-pg., 2021-11-25. (18/06201-1, 18/08131-0, 17/01102-2, 17/26223-7, 16/11541-0, 18/09652-4, 18/21959-8, 19/17488-2, 17/06731-8)