title: Babesia divergens apical membrane antigen-1 (BdAMA-1): A poorly polymorphic protein that induces a weak and late immune response.
abstract: Babesiosis is an important veterinary and zoonotic tick borne disease caused by the hemoprotozoan Babesia spp. which infects red blood cell of its vertebrate host. In order to control the infection, vaccination that targets molecules involved in the invasion process of red blood cells could provide a good alternative to chemotherapy. Among these molecules, Apical Membrane Antigen-1 (AMA-1) has been described as an excellent vaccine candidate in Plasmodium spp. In this paper, we have investigated AMA-1 of Babesia divergens (BdAMA-1) as vaccine candidate by evaluating its polymorphism and by studying the humoral response against BdAMA-1 of sheep experimentally infected with B. divergens. Polymorphism of BdAMA-1 was investigated by sequencing the corresponding gene of 9 B. divergens isolates from different geographical areas in France. Two Bdama-1 haplotypes (A and B) could be defined based on 2 non-synonymous point mutations. In silico prediction of linear epitopes revealed that the antigenicity of the 2 haplotypes is very similar. Antibody production against the extracellular domain of BdAMA-1 is weak and late, between 1 and 5 months after the inoculation of parasites. Both IgG1 and IgG2 are components of the anti-BdAMA-1 response. These results indicate that while BdAMA-1 may not be an immuno-dominant antigen, it could induce a mixed type 1 and type 2 immune response. In light of these results, the potential of BdAMA-1 as vaccine candidate is discussed.
authors.affiliation: Oniris, Ecole nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique, UMR Biologie, Epidémiologie et Analyse de Risque en santé animale, LUNAM Université, CS 40706, Nantes F-44307, France; UMR 1300 BioEpAR, INRA, Nantes F-44307, France. Electronic address: emmanuelle.moreau@oniris-nantes.fr.
authors.forename: E
authors.initials: E
authors.lastname: Moreau
authors.affiliation: Oniris, Ecole nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique, UMR Biologie, Epidémiologie et Analyse de Risque en santé animale, LUNAM Université, CS 40706, Nantes F-44307, France; UMR 1300 BioEpAR, INRA, Nantes F-44307, France.
authors.forename: C
authors.initials: C
authors.lastname: Bonsergent
authors.affiliation: Oniris, Ecole nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique, UMR Biologie, Epidémiologie et Analyse de Risque en santé animale, LUNAM Université, CS 40706, Nantes F-44307, France; UMR 1300 BioEpAR, INRA, Nantes F-44307, France.
authors.forename: I
authors.initials: I
authors.lastname: Al Dybiat
authors.affiliation: Parasitology Department, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Gonzalez
authors.affiliation: Department of Blood-Borne Parasites, Lindsley F. Kimball Research Institute, The New York Blood Center, New York, New York 10065, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lobo
authors.affiliation: Parasitology Department, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Montero
authors.affiliation: Oniris, Ecole nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique, UMR Biologie, Epidémiologie et Analyse de Risque en santé animale, LUNAM Université, CS 40706, Nantes F-44307, France; UMR 1300 BioEpAR, INRA, Nantes F-44307, France.
authors.forename: L
authors.initials: L
authors.lastname: Malandrin
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D001403:Babesia / Q000235:genetics / Q000276:immunology*; D001404:Babesiosis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D002417:Cattle; D016054:DNA, Protozoan / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology / Q000592:standards; D011994:Recombinant Proteins / Q000276:immunology; D016415:Sequence Alignment; D012756:Sheep
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins
keywords: Antibodies; Apical membrane antigen; Babesia divergens; Immune response; Polymorphism; Vaccine