Antibody targeting of a specific region of Pfs47 blocks Plasmodium falciparum malaria transmission

NPJ Vaccines
Gaspar E CanepaCarolina Barillas-Mury

Abstract

Transmission-blocking vaccines are based on eliciting antibody responses in the vertebrate host that disrupt parasite development in the mosquito vector and prevent malaria transmission. The surface protein Pfs47 is present in Plasmodium falciparum gametocytes and female gametes. The potential of Pfs47 as a vaccine target was evaluated. Soluble full-length recombinant protein, consisting of three domains, was expressed in E. coli as a thioredoxin fusion (T-Pfs47). The protein was immunogenic, and polyclonal and monoclonal antibodies (mAb) were obtained, but they did not confer transmission blocking activity (TBA). All fourteen mAb targeted either domains 1 or 3, but not domain 2 (D2), and immune reactivity to D2 was also very low in polyclonal mouse IgG after T-Pfs47 immunization. Disruption of the predicted disulfide bond in D2, by replacing cysteines for alanines (C230A and C260A), allowed expression of recombinant D2 protein in E. coli. A combination of mAbs targeting D2, and deletion proteins from this domain, allowed us to map a central 52 amino acid (aa) region where antibody binding confers strong TBA (78-99%). This 52 aa antigen is immunogenic and well conserved, with only seven haplotypes world-wide that share 96-98% i...Continue Reading

References

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Citations

Dec 17, 2019·Immunological Reviews·Roos M de JongTeun Bousema
Feb 1, 2020·Immunology and Cell Biology·Elizabeth H AitkenStephen J Rogerson
Nov 16, 2019·Scientific Reports·Lampouguin Yenkoidiok-DoutiCarolina Barillas-Mury
Jul 18, 2019·NPJ Vaccines·Puthupparampil V ScariaPatrick E Duffy
Aug 30, 2019·Nature Reviews. Immunology·Jean-Philippe Julien, Hedda Wardemann
Apr 10, 2019·Infection and Immunity·Festus K AcquahLinda E Amoah
Oct 23, 2019·Frontiers in Immunology·Bergeline C Nguemwo TentokamCamila H Coelho
Jan 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Alvaro Molina-CruzCarolina Barillas-Mury
Mar 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Chiamaka V UkegbuDina Vlachou
Jul 29, 2020·Frontiers in Microbiology·Lampouguin Yenkoidiok-DoutiCarolina Barillas-Mury
Jan 13, 2021·Expert Review of Vaccines·Palak N Patel, Niraj Tolia
Jan 23, 2021·Expert Review of Vaccines·Patrick E Duffy
Feb 6, 2021·Vaccines·José Manuel LozanoJuan Edilberto Rincón
Feb 23, 2021·ACS Biomaterials Science & Engineering·Lampouguin Yenkoidiok-DoutiChristopher M Jewell
Dec 15, 2020·ACS Biomaterials Science & Engineering·Lampouguin Yenkoidiok-Douti, Christopher M Jewell

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Datasets Mentioned

BETA
ALQ44015.1

Methods Mentioned

BETA
ELISA
PCR
ion exchange chromatography
size exclusion chromatography
light microscopy

Software Mentioned

GraphPad
Prism
Bepipred
Bepipred Linear Epitope Prediction
GenScript

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