Genetic polymorphism of circumsporozoite protein of Plasmodium falciparum among Chinese migrant workers returning from Africa to Henan Province

Abstract

Background Plasmodium falciparum malaria is recognized as a major global public health problem. The malaria vaccine was important because the case fatality rate of falciparum malaria was high. Plasmodium falciparum circumsporozoite protein (PfCSP) is one of the potential vaccine candidates, but the genetic polymorphism of PfCSP raises concerns regarding the efficacy of the vaccine. This study aimed to investigate the genetic polymorphism of PfCSP and provide data for the improvement of PfCSP-based vaccine (RTS,S malaria vaccine). Methods Blood samples were collected from 287 Chinese migrant workers who were infected with P. falciparum and returning from Africa to Henan Province during 2016–2018. The Pfcsp genes were analysed to estimate the genetic diversity of this parasite. Results The results showed that there were two mutations at the N-terminus of imported Pfcsp in Henan Province, including insertion amino acids (58.71%, 118/201) and A → G (38.81%, 78/201). The number of repeats of tetrapeptide motifs (NANP/NVDP/NPNP/NVDA) in the central repeat region ranged mainly from 39 to 42 (97.51%, 196/201). A total of 14 nonsynonymous amino acid changes were found at the C-terminus. The average nucleotide difference (K) of imported Pfcsp in Henan Province was 5.719, and the haplotype diversity (Hd) was 0.964 ± 0.004. The estimated value of dN-dS was 0.047, indicating that the region may be affected by positive natural selection. The minimum number of recombination events (Rm) of imported Pfcsp in Henan Province was close to that in Africa. The analysis of genetic differentiation showed that there may be moderate differentiation between East Africa and North Africa (Fst = 0.06484), and the levels of differentiation in the other regions were very small (Fst < 0.05). Conclusions The N-terminus of Pfcsp was relatively conserved, and the central repeat region and the Th2R and Th3R regions of the C-terminus were highly polymorphic. The gene polymorphism pattern among Chinese migrant workers returning from Africa to Henan Province was consistent with that in Africa. The geographical pattern of population differentiation and the evidence of natural selection and gene recombination suggested that the effect of polymorphism on the efficacy of PfCSP-based vaccines should be considered.

Genetic polymorphism and evidence of signatures of selection in the Plasmodium falciparum circumsporozoite protein gene in Tanzanian regions with different malaria endemicity

“…However, in Tanzanian isolates, only 2% of the Pfcsp haplotypes matched those of the 3D7 strain, and 0.4% matched the NF54 strain. Low matching of the 3D7/NF54 to the natural Pfcsp is consistent with other studies conducted across Africa and worldwide, which demonstrate low 3D7 haplotypes and little population structure [ 8 , 38 , 64 , 68 ]. However, other studies of the genetic diversity and protective efficacy of the RTS,S/AS01 vaccine suggested that high levels of mismatch between natural isolates and 3D7 may weaken vaccine efficacy [ 28 , 68 ].…”

“…Similar findings were reported in Ghana where pfcsp sequences collected from two sites located over 784 km apart showed a largely homogeneous population with F ST below 0.05, and without any population structure as detected by PCA [ 62 ]. This and other studies of the Pfcsp gene suggested a continued gene flow among parasites or human population mixing between the areas which might have contributed to the observed findings [ 62 , 64 , 65 ]. High genetic diversity and a lack of population differentiation may have important implications related to the efficacy and emergence as well spread of vaccine-resistant parasites [ 66 , 67 ].…”

“…Moreover, the high degree of location-specific Pfcsp diversity observed in Tanzania might result in differences in vaccine efficacy, potentially reducing the effectiveness of the RTS,S/AS01 and R21 vaccines. Monitoring of differential vaccine efficacy according to Pfcsp haplotypes during RTS,S/AS01 and R21 implementation programmes will be valuable, particularly in high transmission areas, where a post-vaccination expansion of non-vaccine haplotypes is likely to be observed which could lead to reduced vaccine efficacy and vaccine breakthrough infections [ 64 ]. Going forward and ensuring the vaccine is efficacious in all endemic areas, the design of malaria vaccines may consider developing a vaccine that works for specific regions based on the genetic architecture of the parasites found in those areas.…”

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

“…Similar findings were reported in Ghana where pfcsp sequences collected from two sites located over 784.4 km apart showed a largely homogeneous population with F ST below 0.05, and without any population structure as detected by PCA (62). This and other studies of the Pfcsp gene suggested a continued gene flow among parasites or human population mixing between the areas which might have contributed to the observed findings (62,64,65). High genetic diversity and a lack of population differentiation may have important implications related to the efficacy and emergence as well spread of vaccine-resistant parasites (66,67).…”

Insecticide resistance of Anopheles sinensis after elimination of malaria in Henan Province, China

“…sinensis at the survey sites, ace-1 and kdr mutation rates and gene mutation rates of the different populations were calculated using the Chi-square ( χ 2 ) test. Nucleotide polymorphism, natural selection and population differentiation were described according to He et al [ 29 ]. In addition, we constructed a haplotype network diagram among the different geographical populations based on the median connection method, with the aim to analyze the genetic relationship among different geographical populations using PopArt software.…”