A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies

Susheel K Singh; Will Roeffen; Gorm Andersen; Teun Bousema; Michael Christiansen; Robert Sauerwein; Michael Theisen

doi:10.1016/j.vaccine.2015.02.040

A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies

Vaccine. 2015 Apr 15;33(16):1981-6. doi: 10.1016/j.vaccine.2015.02.040. Epub 2015 Feb 26.

Authors

Susheel K Singh¹, Will Roeffen², Gorm Andersen³, Teun Bousema⁴, Michael Christiansen⁵, Robert Sauerwein², Michael Theisen⁶

Affiliations

¹ Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
² Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
³ Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Immunology & Infection, London School of Hygiene & Tropical Medicine, London, United Kingdom.
⁵ Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
⁶ Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: mth@ssi.dk.

PMID: 25728318
DOI: 10.1016/j.vaccine.2015.02.040

Abstract

The sexual stage Pfs48/45 antigen is a well-established lead candidate for a transmission blocking (TB) vaccine because of its critical role in parasite fertilization. We have recently produced the carboxy-terminal 10C-fragment of Pfs48/45 containing three known epitopes for TB antibodies as a chimera with the N-terminal region of GLURP (R0). The resulting fusion protein elicited high titer TB antibodies in rodents. To increase the relatively low yield of correctly folded Pfs48/45 we have generated a series of novel chimera truncating the 10C-fragments to 6 cysteine residues containing sub-units (6C). All constructs harbor the major epitope I for TB antibodies. One of these sub-units (R0.6Cc), produced high yields of correctly folded conformers, which could be purified by a simple 2-step procedure. Purified R0.6Cc was stable and elicits high titer TB antibodies in rats. The yield, purity and stability of R0.6Cc allows for further clinical development.

Keywords: GLURP; Pfs48/45; Plasmodium falciparum; SMFA; Transmission blocking.

Publication types

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

MeSH terms

Animals
Antibodies, Blocking / immunology*
Antibodies, Protozoan / immunology*
Antigens, Protozoan / chemistry
Antigens, Protozoan / genetics
Antigens, Protozoan / immunology*
Epitopes / chemistry
Epitopes / genetics
Epitopes / immunology*
Gene Expression
Malaria, Falciparum / prevention & control*
Malaria, Falciparum / transmission
Plasmodium falciparum / immunology*
Protozoan Proteins / chemistry
Protozoan Proteins / genetics
Protozoan Proteins / immunology*
Rats
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / immunology

Substances

Antibodies, Blocking
Antibodies, Protozoan
Antigens, Protozoan
Epitopes
Protozoan Proteins
Recombinant Fusion Proteins