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

Abstract

Pfs230, surface protein of gametocyte/gamete of the human malaria parasite, Plasmodium falciparum, is a prime candidate of malaria transmission-blocking vaccine. P. 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 seven Plasmodium species revealed two distinctive parts: an interspecies variable part (IVP) containing species-specific oligopeptide repeats at the N-terminus and a 7.5 kb 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 resulting 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.

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

“…54 Currently, the development of transmission-blocking vaccines focuses on potential antibodies that interfere with transmission and several candidate antigens are being tested. [55][56][57][58] We also hypothesize that parasite reproductive behavior is guided by the parasite's nutritional milieu, i.e., the nutritional status of the host. 59 These many factors all play a role in the complex, dynamic process of transmission, and warrant further study in the pursuit of developing better tools with which to combat the burden of malaria on infected people and societies.…”

Functional characterization of Plasmodium berghei PSOP25 during ookinete development and as a malaria transmission-blocking vaccine candidate

“…For oocyst quantifications, mice at 3 days p.i. with each parasite line were fed to starved A. stephensi mosquitoes for 30 min [36, 37]. Ten days after feeding, ~ 30 fed mosquitoes from each genotype were dissected for counting of the number of oocysts per infected mosquito and to determine the prevalence and intensity of infection.…”

Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization

“…In the case of P. vivax TBV, characterized antigens include two zygote/ookinete surface proteins, Pvs25 and Pvs28 [17,[30][31][32], and one gametocyte/gamete surface protein, Pvs230 [33,34]. Although transmission-blocking immunity in humans in endemic areas against gametocyte/gamete surface proteins has been reported [35][36][37], there is no report that describes the presence of the pre-fertilization stage TBV candidate molecules of P. vivax other than the Pvs230.…”