Immune response and protective profile elicited by a multi-epitope chimeric protein derived from Leptospira interrogans.
BACKGROUND
Pathogenic Leptospira is the causative agent of leptospirosis, a widely disseminated disease of human and veterinary concern. The development of vaccines that elicit cross-protective immunity through multiple leptospiral serovars has long been pursued. The aim of this study was to develop a novel chimeric multi-epitope fusion antigen, containing sequences of previously studied outer membrane proteins (OMPs) of Leptospira.


METHODS
The chimeric protein was designed based on the amino acid sequences of the LigA, Mce, Lsa45, OmpL1, and LipL41 proteins, cloned into pAE vector, the protein expressed in Escherichia coli, and its immune response evaluated in the hamster infection model.


RESULTS
The recombinant chimeric protein (rChi) was recognized by antibodies present in serum samples of confirmed cases of human leptospirosis and experimentally infected hamsters, demonstrating that the rChi protein participates in the immune response activation during infection. However, despite high antibody titers achieved when the rChi protein was administered with either Alhydrogel or Bordetella pertussis monophosphoryl lipid A (MPLA), only 50% of the hamsters were protected against infection.


CONCLUSIONS
Although a complete characterization of the immune response elicited by rChi/adjuvant in hamsters is required, it is believed that the construction of chimeric genes is an important attempt towards the generation of an effective vaccine against leptospirosis.
Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 Sao Paulo, SP, Brazil; Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Sao Paulo, SP, Brazil.
Luis G V
LGV
Fernandes
Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 Sao Paulo, SP, Brazil; Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Sao Paulo, SP, Brazil.
Aline F
AF
Teixeira
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Sao Paulo, SP, Brazil.
Antonio F S
AFS
Filho
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Sao Paulo, SP, Brazil.
Gisele O
GO
Souza
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Sao Paulo, SP, Brazil.
Silvio A
SA
Vasconcellos
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Sao Paulo, SP, Brazil.
Marcos B
MB
Heinemann
Centro de Bacteriología, Instituto Adolfo Lutz, Sao Paulo, SP, Brazil.
Eliete C
EC
Romero
Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 Sao Paulo, SP, Brazil; Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Sao Paulo, SP, Brazil. Electronic address: ana.nascimento@butantan.gov.br.
Ana L T O
ALTO
Nascimento
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D006224:Cricetinae; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007921:Leptospira interrogans / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic
Chimeric protein; Leptospira; Leptospirosis; Vaccine