Analysis of von Willebrand factor A domain-related protein (WARP) polymorphism in temperate and tropical Plasmodium vivax field isolates

Saber Gholizadeh,Sedigheh Zakeri,Navid Dinparast Djadid,Hamid Reza Basseri,Hossein Ladoni

doi:10.1186/1475-2875-8-137

Saber Gholizadeh, Sedigheh Zakeri + Show 3 more

Open Access

https://doi.org/10.1186/1475-2875-8-137

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Abstract

BackgroundThe identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs), among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP), is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran.MethodsClinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991) which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp.ResultsAmplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT) to A (GCT) and R (AGA) to S (AGT)] in comparison with the Sal-I sequence.ConclusionThis study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

Highlights

The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs), among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets
One of the TBV targets is a soluble protein that is called von Willebrand factor A domain-related protein (WARP), which is expressed in late ookinetes and early oocysts [14,15]
This study presents the first large-scale survey on PvWARP polymorphism in the world, that provides a baseline data for developing WARP-based TBV against both temparate and tropical P. vivax isolates

Summary

Introduction

The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs), among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. The sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP), is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. One of the TBV targets is a soluble protein that is called von Willebrand factor A domain-related protein (WARP), which is expressed in late ookinetes and early oocysts [14,15]. Oocyst formation was reduced significantly when mosquitoes fed on an infected mouse passively immunized with the antiWARP antibody. This indicates that the antibody interferes with WARP function by recognizing the protein on the surface of the parasite and makes it a candidate antigen for a TBV [14]

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