Signatures of selection and drivers for novel mutation on transmission-blocking vaccine candidate Pfs25 gene in western Kenya
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Date
2022-04
Authors
Ochwedo, Kevin O.
Onyango, Shirley A.
Omondi, Collince J.
Orondo, Pauline W.
Ondeto, Benyl M.
Lee, Ming-Chieh
Atieli, Harrysone E.
Ogolla, Sidney O.
Githeko, Andrew K.
Otieno, Antony C. A.
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS ONE
Abstract
Background
Leading transmission-blocking vaccine candidates such as Plasmodium falciparum surface protein 25 (Pfs25 gene) may undergo antigenic alterations which may render them ineffective or allele-specific. This study examines the level of genetic diversity, signature of selection and drivers of Pfs25 polymorphisms of parasites population in regions of western Kenya with varying malaria transmission intensities.
Methods
Dry blood spots (DBS) were collected in 2018 and 2019 from febrile outpatients with malaria at health facilities in malaria-endemic areas of Homa Bay, Kisumu (Chulaimbo) and the epidemic-prone highland area of Kisii. Parasites DNA were extracted from DBS using Chelex method. Species identification was performed using real-time PCR. The 460 base pairs (domains 1–4) of the Pfs25 were amplified and sequenced for a total of 180 P. falciparuminfected blood samples.
Results
Nine of ten polymorphic sites were identified for the first time. Overall, Pfs25 exhibited low nucleotide diversity (0.04×10−2) and low mutation frequencies (1.3% to 7.7%). Chulaimbo had the highest frequency (15.4%) of mutated sites followed by Kisii (6.7%) and Homa Bay (5.1%). Neutrality tests of Pfs25 variations showed significant negative values of Tajima’s D (-2.15, p<0.01) and Fu’s F (-10.91, p<0.001) statistics tests. Three loci pairs (123, 372), (364, 428) and (390, 394) were detected to be under linkage disequilibrium and none hadhistory of recombination. These results suggested that purifying selection and inbreeding might be the drivers of the observed variation in Pfs25.
Conclusion
Given the low level of nucleotide diversity, it is unlikely that a Pfs25 antigen-based vaccine would be affected by antigenic variations. However, continued monitoring of Pfs25 immunogenic domain 3 for possible variants that might impact vaccine antibody binding is warranted.
Description
Research paper in PLoS ONE 17(4): e0266394.https://doi.org/10.1371/journal. pone.0266394
Keywords
Citation
Citation:Ochwedo KO, Onyango SA, Omondi CJ, Orondo PW, Ondeto BM, Lee M-C, et al. (2022) Signatures of selection and drivers for novel mutation on transmission-blocking vaccine candidate Pfs25 gene in western Kenya. PLoSONE 17(4): e0266394.https://doi.org/10.1371/journal. pone.0266394