title: A recombinant multi-antigen vaccine formulation containing Babesia bovis merozoite surface antigens MSA-2a1, MSA-2b and MSA-2c elicits invasion-inhibitory antibodies and IFN-γ producing cells.
abstract: Babesia bovis is a tick-transmitted protozoan hemoparasite and the causative agent of bovine babesiosis, a potential risk to more than 500 million cattle worldwide. The vaccines currently available are based on attenuated parasites, which are difficult to produce, and are only recommended for use in bovines under one year of age. When used in older animals, these vaccines may cause life-threatening clinical symptoms and eventually death. The development of a multi-subunit recombinant vaccine against B. bovis would be attractive from an economic standpoint and, most importantly, could be recommended for animals of any age. In the present study, recombinant ectodomains of MSA-2a1, MSA-2b and MSA-2c antigens were expressed in Pichia pastoris yeast as secreted soluble peptides.
  
  
  
  The antigens were purified to homogeneity, and biochemically and immunologically characterized. A vaccine formulation was obtained by emulsifying a mixture of the three peptides with the adjuvant Montanide ISA 720, which elicited high IgG antibody titers against each of the above antigens. IgG antibodies generated against each MSA-antigen recognized merozoites and significantly inhibited the invasion of bovine erythrocytes. Cellular immune responses were also detected, which were characterized by splenic and lymph node CD4+T cells producing IFN-γ and TNF-α upon stimulation with the antigens MSA-2a1or MSA-2c.
  
  
  
  These data strongly suggest the high protective potential of the presented formulation, and we propose that it could be tested in vaccination trials of bovines challenged with B. bovis.
authors.affiliation: CTCMOL, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol, 207, São Paulo, 04044-010, SP, Brazil.
authors.forename: Alba Marina
authors.initials: AM
authors.lastname: Gimenez
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil.
authors.forename: Katia S
authors.initials: KS
authors.lastname: Françoso
authors.affiliation: CTCMOL, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol, 207, São Paulo, 04044-010, SP, Brazil.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Ersching
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, CEP 04023-062, São Paulo, Brazil.
authors.forename: Marcelo Y
authors.initials: MY
authors.lastname: Icimoto
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, CEP 04023-062, São Paulo, Brazil.
authors.forename: Vitor
authors.initials: V
authors.lastname: Oliveira
authors.affiliation: Instituto de Patobiologia, CICVyA, INTA-Castelar, 1686, Hurlingham, Argentina.
authors.forename: Anabel E
authors.initials: AE
authors.lastname: Rodriguez
authors.affiliation: Instituto de Patobiologia, CICVyA, INTA-Castelar, 1686, Hurlingham, Argentina.|CONICET, C1033AAJ, Ciudad Autonoma de Buenos Aires, Argentina.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Schnittger
authors.affiliation: Instituto de Patobiologia, CICVyA, INTA-Castelar, 1686, Hurlingham, Argentina.|CONICET, C1033AAJ, Ciudad Autonoma de Buenos Aires, Argentina.
authors.forename: Monica
authors.initials: M
authors.lastname: Florin-Christensen
authors.affiliation: CTCMOL, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol, 207, São Paulo, 04044-010, SP, Brazil.
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil. isoares@usp.br.
authors.forename: Irene S
authors.initials: IS
authors.lastname: Soares
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D009829:Oleic Acids / Q000008:administration & dosage; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; C476548:MSA-2 protein, Babesia bovis; D008565:Membrane Proteins; D009829:Oleic Acids; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C001681:mannide monooleate; D008353:Mannitol; D007371:Interferon-gamma
keywords: Babesia bovis; Merozoites; Recombinant vaccine