A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria

Abstract Pfs48/45 is a leading antigen candidate for a transmission blocking (TB) vaccine. However, efforts to produce affordable, safe and correctly folded full-length Pfs48/45 using different protein expression systems have not produced an antigen with satisfactory TB activity. Pfs48/45 has 16 cys...

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Autores principales:	Tarlan Mamedov, Kader Cicek, Kazutoyo Miura, Burcu Gulec, Ersin Akinci, Gunay Mammadova, Gulnara Hasanova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/22aae6d0416149a0812a6da6f778735d
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spelling	oai:doaj.org-article:22aae6d0416149a0812a6da6f778735d2021-12-02T15:08:31ZA Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria10.1038/s41598-019-46375-62045-2322https://doaj.org/article/22aae6d0416149a0812a6da6f778735d2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46375-6https://doaj.org/toc/2045-2322Abstract Pfs48/45 is a leading antigen candidate for a transmission blocking (TB) vaccine. However, efforts to produce affordable, safe and correctly folded full-length Pfs48/45 using different protein expression systems have not produced an antigen with satisfactory TB activity. Pfs48/45 has 16 cysteines involved in disulfide bond formation, and the correct formation is critical for proper folding and induction of TB antibodies. Moreover, Pfs48⁄45 is not a glycoprotein in the native hosts, but contains potential glycosylation sites, which are aberrantly glycosylated during expression in eukaryotic systems. Here, we demonstrate for the first time that full length, Endo H in vivo enzymatic deglycosylated Pfs48/45 antigen is produced at a high level in plants and is structurally stable at elevated temperatures. Sera from mice immunized with this antigen showed strong inhibition in SMFA. Thus, Endo H in vivo enzymatic deglycosylated Pfs48/45 is a promising candidate for the development of an affordable TB vaccine, which may have the potential to save millions.Tarlan MamedovKader CicekKazutoyo MiuraBurcu GulecErsin AkinciGunay MammadovaGulnara HasanovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tarlan Mamedov Kader Cicek Kazutoyo Miura Burcu Gulec Ersin Akinci Gunay Mammadova Gulnara Hasanova A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria
description	Abstract Pfs48/45 is a leading antigen candidate for a transmission blocking (TB) vaccine. However, efforts to produce affordable, safe and correctly folded full-length Pfs48/45 using different protein expression systems have not produced an antigen with satisfactory TB activity. Pfs48/45 has 16 cysteines involved in disulfide bond formation, and the correct formation is critical for proper folding and induction of TB antibodies. Moreover, Pfs48⁄45 is not a glycoprotein in the native hosts, but contains potential glycosylation sites, which are aberrantly glycosylated during expression in eukaryotic systems. Here, we demonstrate for the first time that full length, Endo H in vivo enzymatic deglycosylated Pfs48/45 antigen is produced at a high level in plants and is structurally stable at elevated temperatures. Sera from mice immunized with this antigen showed strong inhibition in SMFA. Thus, Endo H in vivo enzymatic deglycosylated Pfs48/45 is a promising candidate for the development of an affordable TB vaccine, which may have the potential to save millions.
format	article
author	Tarlan Mamedov Kader Cicek Kazutoyo Miura Burcu Gulec Ersin Akinci Gunay Mammadova Gulnara Hasanova
author_facet	Tarlan Mamedov Kader Cicek Kazutoyo Miura Burcu Gulec Ersin Akinci Gunay Mammadova Gulnara Hasanova
author_sort	Tarlan Mamedov
title	A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria
title_short	A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria
title_full	A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria
title_fullStr	A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria
title_full_unstemmed	A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria
title_sort	plant-produced in vivo deglycosylated full-length pfs48/45 as a transmission-blocking vaccine candidate against malaria
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/22aae6d0416149a0812a6da6f778735d
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A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria

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