Genetic polymorphism of merozoite surface protein-3 in Myanmar Plasmodium falciparum field isolates

Abstract

Background Plasmodium falciparum merozoite surface protein-3 (PfMSP-3) is a target of naturally acquired immunity against P. falciparum infection and is a promising vaccine candidate because of its critical role in the erythrocyte invasion of the parasite. Understanding the genetic diversity of pfmsp-3 is important for recognizing genetic nature and evolutionary aspect of the gene in the natural P. falciparum population and for designing an effective vaccine based on the antigen. Methods Blood samples collected from P. falciparum-infected patients in Naung Cho and Pyin Oo Lwin, Myanmar, in 2015 were used in this study. The pfmsp-3 was amplified by polymerase chain reaction, cloned, and sequenced. Genetic polymorphism and natural selection of Myanmar pfmsp-3 were analysed using the programs DNASTAR, MEGA6, and DnaSP 5.10.00. Genetic diversity and natural selection of the global pfmsp-3 were also comparatively analysed. Results Myanmar pfmsp-3 displayed 2 different alleles, 3D7 and K1. The 3D7 allelic type was predominant in the population, but genetic polymorphism was less diverse than for the K1 allelic type. Polymorphic characters in both allelic types were caused by amino acid substitutions, insertions, and deletions. Amino acid substitutions were mainly occurred at the alanine heptad repeat domains, whereas most insertions and deletions were found at the glutamate rich domain. Overall patterns of amino acid polymorphisms detected in Myanmar pfmsp-3 were similar in the global pfmsp-3 population, but novel amino acid changes were observed in Myanmar pfmsp-3 with low frequencies. Complicated patterns of natural selection and recombination events were predicted in the global pfmsp-3, which may act as major driving forces to maintain and generate genetic diversity of the global pfmsp-3 population. Conclusion Global pfmsp-3 revealed genetic polymorphisms, suggesting that the functional and structural consequences of the polymorphisms should be considered in designing a vaccine based on PfMSP-3. Further examination of genetic diversity of pfmsp-3 in the global P. falciparum population is necessary to gain in-depth insight for the population structure and evolutionary aspect of global pfmsp-3.

Genetic polymorphism and evidence of signatures of selection in thePlasmodium falciparumcircumsporozoite protein gene in Tanzanian regions with different malaria endemicity

“…The current RTS,S, recombinant vaccine was constructed with pfcsp of P. falciparum 3D7 strain, but in Tanzanian isolates, only 0.7% 3D7-matched Tanzanian pfcsp haplotypes. Low matching of the 3D7 to the natural Pfcsp has been reported in many other studies in Africa (8,38,64,68). This data is consistent with other studies conducted across Africa and worldwide, which demonstrate low 3D7 haplotypes and little population structure.…”

“…The overall nucleotide diversity was 0.0035 with Muleba showing a high peak in Th2R epitopes. A similar pattern of nucleotide polymorphism was found in other African countries including Malawi, The Gambia, Nigeria, Ghana, Mali and Guinea (8,38,62).…”

“…Reports from previous studies of the population structure of P. falciparum genes coding for vaccine antigens, including the Pfcsp showed variable levels of diversity and geographic restriction of specific subgroups which may have an impact on the efficacy of malaria vaccines based on this gene in specific geographic regions (36). In particular, comparative diversity studies of the 3D7 Pfcsp gene showed that only 0.2% to 5.0% of the vaccine strains matched the global Pfcsp gene (38). A larger number of these studies described polymorphisms in the Pfcsp gene at the global level, with limited local-specific studies.…”

Genetic diversity of Plasmodium falciparum erythrocyte membrane protein 1 in field isolates from central Myanmar

“…In addition, the level of malaria transmission in Myanmar varies by region, making the regional persistence of the disease heterogeneous [19][20][21][22]. Therefore, understanding the genetic diversity of malaria parasites represents a major step toward disease eradication because it can provide insights into effective vaccine development.…”

Targeting the Plasmodium falciparum proteome and organelles for potential antimalarial drug candidates

“…The prevalence of antibodies against the Pf antigen offers promise as a key to gain immunity ( Ondigo et al, 2020 ). Notably, MSP1 ( Jäschke et al, 2017 ; Thái et al, 2018 ), MSP2 ( Das et al, 2017 ; Eacret et al, 2019 ; Lu et al, 2019 ; MacRaild et al, 2011 ), MSP3 ( Lê et al, 2020 ), and MSP4 ( Deshmukh et al, 2018 ; Perraut et al, 2017 ), and MSP10 ( Bendezu et al, 2019 ; Nagaoka et al, 2019 ) are blood-stage proteins that serve as promising vaccine candidates as their-specific antibodies have shown protection against malaria. The parasite leverages SUB1 protease to cleave MSP1 into fragments prior to egress ( Koussis et al, 2009 ).…”