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

Vaccine
Susheel K SinghMichael Theisen

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.

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Citations

Oct 16, 2015·Vaccine·Simon J DraperSumi Biswas
Jan 4, 2017·Expert Review of Vaccines·Michael TheisenRobert Sauerwein
Jul 13, 2017·Expert Review of Vaccines·Michael TheisenSubhash Singh
Oct 29, 2017·Molecular & Cellular Proteomics : MCP·Corrie OrtegaChristoph Grundner
Jan 3, 2019·Expert Review of Vaccines·K L WilsonM Plebanski
Dec 17, 2019·Immunological Reviews·Roos M de JongTeun Bousema
Apr 10, 2019·Infection and Immunity·Festus K AcquahLinda E Amoah
Oct 28, 2018·Nature Communications·Prasun KunduJean-Philippe Julien
Dec 4, 2019·The Journal of Biological Chemistry·Susheel K SinghMichael Theisen
Jan 13, 2021·Expert Review of Vaccines·Palak N Patel, Niraj Tolia
Jan 23, 2021·Expert Review of Vaccines·Patrick E Duffy
Dec 3, 2016·International Journal for Parasitology·Silvia A Arredondo, Stefan H I Kappe

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