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 Background 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 re...

Full description

Bibliographic Details
Main Authors: Alba Marina Gimenez, Katia S. Françoso, Jonatan Ersching, Marcelo Y. Icimoto, Vitor Oliveira, Anabel E. Rodriguez, Leonhard Schnittger, Monica Florin-Christensen, Mauricio M. Rodrigues, Irene S. Soares
Format: Article
Language:English
Published: BMC 2016-11-01
Series:Parasites & Vectors
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13071-016-1862-1
id doaj-b2452397f4b24829b548625b537b011d
record_format Article
spelling doaj-b2452397f4b24829b548625b537b011d2020-11-24T22:17:01ZengBMCParasites & Vectors1756-33052016-11-019111310.1186/s13071-016-1862-1A 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 cellsAlba Marina Gimenez0Katia S. Françoso1Jonatan Ersching2Marcelo Y. Icimoto3Vitor Oliveira4Anabel E. Rodriguez5Leonhard Schnittger6Monica Florin-Christensen7Mauricio M. Rodrigues8Irene S. Soares9CTCMOL, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de MedicinaDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São PauloCTCMOL, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de MedicinaDepartamento de Biofísica, Universidade Federal de São PauloDepartamento de Biofísica, Universidade Federal de São PauloInstituto de Patobiologia, CICVyA, INTA-CastelarInstituto de Patobiologia, CICVyA, INTA-CastelarInstituto de Patobiologia, CICVyA, INTA-CastelarCTCMOL, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de MedicinaDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São PauloAbstract Background 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. Results 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-2a1 or MSA-2c. Conclusions 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.http://link.springer.com/article/10.1186/s13071-016-1862-1Babesia bovisMerozoitesRecombinant vaccine
collection DOAJ
language English
format Article
sources DOAJ
author Alba Marina Gimenez
Katia S. Françoso
Jonatan Ersching
Marcelo Y. Icimoto
Vitor Oliveira
Anabel E. Rodriguez
Leonhard Schnittger
Monica Florin-Christensen
Mauricio M. Rodrigues
Irene S. Soares
spellingShingle Alba Marina Gimenez
Katia S. Françoso
Jonatan Ersching
Marcelo Y. Icimoto
Vitor Oliveira
Anabel E. Rodriguez
Leonhard Schnittger
Monica Florin-Christensen
Mauricio M. Rodrigues
Irene S. Soares
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
Parasites & Vectors
Babesia bovis
Merozoites
Recombinant vaccine
author_facet Alba Marina Gimenez
Katia S. Françoso
Jonatan Ersching
Marcelo Y. Icimoto
Vitor Oliveira
Anabel E. Rodriguez
Leonhard Schnittger
Monica Florin-Christensen
Mauricio M. Rodrigues
Irene S. Soares
author_sort Alba Marina Gimenez
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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher BMC
series Parasites & Vectors
issn 1756-3305
publishDate 2016-11-01
description Abstract Background 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. Results 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-2a1 or MSA-2c. Conclusions 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.
topic Babesia bovis
Merozoites
Recombinant vaccine
url http://link.springer.com/article/10.1186/s13071-016-1862-1
work_keys_str_mv AT albamarinagimenez arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT katiasfrancoso arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT jonatanersching arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT marceloyicimoto arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT vitoroliveira arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT anabelerodriguez arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT leonhardschnittger arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT monicaflorinchristensen arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT mauriciomrodrigues arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT irenessoares arecombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT albamarinagimenez recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT katiasfrancoso recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT jonatanersching recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT marceloyicimoto recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT vitoroliveira recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT anabelerodriguez recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT leonhardschnittger recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT monicaflorinchristensen recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT mauriciomrodrigues recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
AT irenessoares recombinantmultiantigenvaccineformulationcontainingbabesiabovismerozoitesurfaceantigensmsa2a1msa2bandmsa2celicitsinvasioninhibitoryantibodiesandifngproducingcells
_version_ 1725787041345568768