Evidence map›Paper›PMID 35390042›Full record

ArticlePloS one2022

Signatures of selection and drivers for novel mutation on transmission-blocking vaccine candidate Pfs25 gene in western Kenya.

Kevin O Ochwedo, Shirley A Onyango, Collince J Omondi, Pauline W Orondo, Benyl M Ondeto, Ming-Chieh Lee, Harrysone E Atieli, Sidney O Ogolla, Andrew K Githeko, Antony C A Otieno and 4 more

Abstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Kevin O OchwedoDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, Kenya.ORCID 0000-0002-4510-8344
Shirley A OnyangoSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, Kenya.
Collince J OmondiDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, Kenya.
Pauline W OrondoSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, Kenya.
Benyl M OndetoDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, Kenya.
Ming-Chieh LeeProgram in Public Health, College of Health Sciences, University of California, Irvine, Irvine, California, United States of America.ORCID 0000-0002-2462-6089
Harrysone E AtieliSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, Kenya.
Sidney O OgollaCentre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Andrew K GithekoSub-Saharan Africa International Centre for Excellence in Malaria Research, Homa Bay, Kenya.
Antony C A OtienoDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, Kenya.
Wolfgang R MukabanaDepartment of Biology, Faculty of Science and Technology, University of Nairobi, Nairobi, Kenya.
Guiyun YanProgram in Public Health, College of Health Sciences, University of California, Irvine, Irvine, California, United States of America.
Daibin ZhongProgram in Public Health, College of Health Sciences, University of California, Irvine, Irvine, California, United States of America.ORCID 0000-0002-2771-9598
James W KazuraCentre for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America.

Funding

Vector Biology of Invasive Anopheles stephensi in Rural to Urban Landscapes in EthiopiaU19AI129326 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Guiyun Yan · 2017 to 2026
$19.9M
Ecology of African Highland MalariaR01AI050243 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI YAN, GUIYUN · 2001 to 2018
$8.8M
Research Training in Mosquito Genomics and Bioinformat*D43TW001505 · FIC · UNIVERSITY OF CALIFORNIA-IRVINE · PI Guiyun Yan · 2000 to 2026
$6.0M
FIC NIH HHS D43 TW001505NIAID NIH HHS R01 AI050243NIAID NIH HHS U19 AI129326
6 · The paper itself

Abstract

backgroundLeading 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.

methodsDry 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. falciparum-infected blood samples.

resultsNine 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 had history of recombination. These results suggested that purifying selection and inbreeding might be the drivers of the observed variation in Pfs25.

conclusionGiven 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.

Indexed as

Malaria VaccinesProtozoan ProteinsSelection, GeneticAntibodies, ProtozoanAntigens, ProtozoanHumansKenyaMalaria, FalciparumMutationNucleotidesPlasmodium falciparumAntibodies, ProtozoanAntigens, ProtozoanMalaria VaccinesNucleotidesPfs25 protein, Plasmodium falciparumProtozoan Proteins

Identifiers

PMID35390042
PMCPMC8989228

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.