Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax.

Masanori Doi (1) , Kazuyuki Tanabe (2) , Shin-Ichiro Tachibana (2) , Meiko Hamai (3) , Mayumi Tachibana (3) , Toshihiro Mita (4) , Masanori Yagi (5) , Fadile Yildiz Zeyrek (6) , Marcelo U Ferreira (7) , Hiroshi Ohmae (8) , Akira Kaneko (9, 10) , Milijaona Randrianarivelojosia (11) , Jetsumon Sattabongkot (12) , Ya-Ming Cao (13) , Toshihiro Horii (5) , Motomi Torii (3, 14) , Takafumi Tsuboi (1, 14, 15)

1 Cell-free Science and Technology Research Center
2 Laboratory of Malariology, Research Institute for Microbial Diseases
3 Department of Molecular Parasitology
4 Department of International Affairs and Tropical Medicine
5 Department of Molecular Protozoology, Research Institute for Microbial Diseases
6 Department of Microbiology
7 IBS - Department of Parasitology [São Paulo]
8 Department of Parasitology
9 Karolinska Institutet [Stockholm]
10 Global COE
11 Institut Pasteur de Madagascar
12 AFRIMS - Armed Forces Research Institute of Medical Sciences [Bangkok]
13 Department of Immunology, College of Basic Medical Sciences
14 Ehime Proteo-Medicine Research Center
15 Venture Business Laboratory

Pfs230, surface protein of gametocyte/gamete of the human malaria parasite, Plasmodium falciparum, is a prime candidate of malaria transmission-blocking vaccine. Plasmodium vivax has an ortholog of Pfs230 (Pvs230), however, there has been no study in any aspects on Pvs230 to date. To investigate whether Pvs230 can be a vivax malaria transmission-blocking vaccine, we performed evolutionary and population genetic analysis of the Pvs230 gene (pvs230: PVX_003905). Our analysis of Pvs230 and its orthologs in eight Plasmodium species revealed two distinctive parts: an interspecies variable part (IVP) containing species-specific oligopeptide repeats at the N-terminus and a 7.5kb interspecies conserved part (ICP) containing 14 cysteine-rich domains. Pvs230 was closely related to its orthologs, Pks230 and Pcys230, in monkey malaria parasites. Analysis of 113 pvs230 sequences obtained from worldwide, showed that nucleotide diversity is remarkably low in the non-repeat 8-kb region of pvs230 (θπ=0.00118) with 77 polymorphic nucleotide sites, 40 of which results in amino acid replacements. A signature of purifying selection but not of balancing selection was seen on pvs230. Functional and/or structural constraints may limit the level of polymorphism in pvs230. The observed limited polymorphism in pvs230 should ground for utilization of Pvs230 as an effective transmission-blocking vaccine.

Domaines: Sciences du Vivant [q-bio]

Masanori Doi, Kazuyuki Tanabe, Shin-Ichiro Tachibana, Meiko Hamai, Mayumi Tachibana, et al.. Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax.. Vaccine, 2011, 29 (26), pp.4308-15. ⟨10.1016/j.vaccine.2011.04.028⟩. ⟨pasteur-00835696⟩