Vaccination against babesiosis using recombinant GPI-anchored proteins

Sarah Nathaly Wieser; Leonhard Schnittger; Monica Florin-Christensen; Stephane Delbecq; Theo Schetters

doi:10.1016/j.ijpara.2018.12.002

Vaccination against babesiosis using recombinant GPI-anchored proteins

Int J Parasitol. 2019 Feb;49(2):175-181. doi: 10.1016/j.ijpara.2018.12.002. Epub 2019 Jan 24.

Authors

Sarah Nathaly Wieser¹, Leonhard Schnittger¹, Monica Florin-Christensen¹, Stephane Delbecq², Theo Schetters³

Affiliations

¹ Institute of Veterinary Pathobiology, National Institutes of Agricultural Technology (INTA)-National Research Council of Argentina (CONICET), Los Reseros y Nicolas Repetto, s/n, 1686 Hurlingham, Prov. Buenos Aires, Argentina.
² Vaccination Anti-Parasitaire (VAP), University of Montpellier, France.
³ Vaccination Anti-Parasitaire (VAP), University of Montpellier, France; Department of Veterinary Tropical Diseases, Veterinary Faculty, University of Pretoria, South Africa. Electronic address: th.schetters@protactivity.com.

PMID: 30684517
DOI: 10.1016/j.ijpara.2018.12.002

Abstract

The increase in human babesiosis is of major concern to health authorities. In the USA, most of these cases are due to infections with Babesia microti, whereas in Europe B. divergens is the major cause of clinical disease in humans. Here we review the immunological and biological literature of glycosylphosphatidylinositol (GPI)-anchored merozoite proteins of human Babesia parasites with emphasis on their role in immunity, and provide some new bioinformatical information on B. microti GPI-Anchored Proteins (GPI-AP). Cattle can be vaccinated with soluble parasite antigens (SPA) of Babesia divergens that are released by the parasite during proliferation. The major component in SPA preparations appeared to be a 37 kDa merozoite surface protein that is anchored in the merozoite membrane by a GPI anchor. Animals could be protected by vaccination with the recombinant 37 kDa protein expressed in Escherichia coli, provided the protein had a hydrophobic terminal sequence. Based on this knowledge, a recombinant vaccine was developed against Babesia canis infection in dogs, successfully. In order to identify similar GPI-AP in B. microti, the genome was analysed. Here it is shown that B. microti encodes all proteins necessary for GPI assembly and its subsequent protein transfer. In addition, in total 21 genes encoding for GPI-AP were detected, some of which reacted particularly strongly with sera from B. microti-infected human patients. Reactivity of antibodies with GPI-anchored merozoite proteins appears to be dependent on the structural conformation of the molecule. It is suggested that the three-dimensional structure of the protein that is anchored in the membrane is different from that of the protein that has been shed from the merozoite surface. The significance of this protein's dynamics in parasite biology and immune evasion is discussed. Finally, we discuss developments in tick and Babesia vaccine research, and the role such vaccines could play in the control of human babesiosis.

Keywords: Apicomplexa; Babesia divergens; Babesia microti; GPI anchors; Human babesiosis; Merozoite surface protein; Recombinant vaccine.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antigens, Protozoan / immunology*
Babesia microti / immunology*
Babesiosis / prevention & control*
Disease Models, Animal
Dogs
Protozoan Vaccines / administration & dosage*
Protozoan Vaccines / immunology*
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / immunology

Substances

Antigens, Protozoan
Protozoan Vaccines
Vaccines, Synthetic