Evidence map›Paper›PMID 27038925›Full record

ArticleParasites & vectors2016

Characterization of a Plasmodium berghei sexual stage antigen PbPH as a new candidate for malaria transmission-blocking vaccine.

Xu Kou, Wenqi Zheng, Feng Du, Fei Liu, Meilian Wang, Qi Fan, Liwang Cui, Enjie Luo, Yaming Cao

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Parasites & vectors, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
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

18 citing papers in PubMed, 31 citations in OpenAlex.

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  10. Identification of Novel Malaria Transmission-Blocking Vaccine Candidates.Frontiers in cellular and infection microbiology · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Xu KouDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China.
Wenqi ZhengDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China.
Feng DuDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China.
Fei LiuDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China.
Meilian WangDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China.
Qi FanDalian Institute of Biotechnology, Dalian, Liaoning, China.
Liwang CuiDepartment of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA.
Enjie LuoDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China. enjieluo@hotmail.com.
Yaming CaoDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110001, China. ymcao@mail.cmu.edu.cn.
China Medical University · CNPennsylvania State University · US

Funding

Puf-Mediated Translation Control in PlasmodiumR01AI104946 · NIAID · PENNSYLVANIA STATE UNIVERSITY, THE · PI CUI, LIWANG · 2014 to 2017
$1.5M
Transmission blocking vaccine study in Plasmodium vivaxR01AI099611 · NIAID · CHINA MEDICAL UNIVERSITY · PI CAO, YAMING · 2012 to 2016
$648k
NIAID NIH HHS R01 AI099611NIAID NIH HHS R01AI099611NIAID NIH HHS R01 AI104946NIAID NIH HHS R01AI104946
6 · The paper itself

Abstract

backgroundTransmission-blocking vaccines (TBVs) are a promising strategy for malaria control and elimination. However, candidate TBV antigens are currently limited, highlighting the urgency of identifying new antigens for TBV development.

methodsUsing a combination of bioinformatic analysis and functional studies in the rodent malaria model Plasmodium berghei, we identified a conserved Plasmodium protein PbPH (PBANKA_041720) containing a pleckstrin homology (PH) domain. The expression of PbPH was detected by Western blot and indirect immunofluorescence assay (IFA). The function of PbPH was tested by genetic knockout. The TB activity was confirmed by in vitro ookinete conversion assay and mosquito feeding.

resultsPbPH was detected in Western blot as highly expressed in sexual stages (gametocytes and ookinetes). IFA revealed localizations of PbPH on the surface of gametes, zygotes, and ookinetes. Deletion of the pbph gene did not affect asexual growth, but significantly reduced the formation of gametocytes, ookinetes, and oocysts, indicating that PbPH protein is required for parasite sexual development. Recombinant PbPH expressed and purified from bacteria elicited strong antibody responses in mice and the antibodies significantly inhibited exflagellation of male gametocytes and formation of ookinetes in a concentration-dependent manner. Mosquito feeding experiments confirmed that mosquitoes fed on mice immunized with PbPH had 13 % reduction in the prevalence of infection and almost 48 % reduction in oocyst density.

conclusionsPbph is a highly conserved Plasmodium gene and is required for parasite sexual development. PbPH protein is expressed on the surface of gametes and ookinetes. Immunization of mice against the recombinant PbPH protein induced strong antibody responses that effectively reduced the formation of male gametes and ookinetes in vitro and blocked transmission of the parasites to mosquitoes. These results highlight PbPH as a potential TBV candidate that is worth future investigations in human malaria parasites.

Indexed as

AnimalsAntigens, ProtozoanBlotting, WesternComputational BiologyDisease Models, AnimalDisease Transmission, InfectiousFluorescent Antibody Technique, IndirectGene Knockout TechniquesMalariaMalaria VaccinesMicePlasmodium bergheiProtozoan ProteinsAntigens, ProtozoanMalaria VaccinesProtozoan ProteinsGametocyteMalariaOokinetePH domain proteinPlasmodium bergheiSexual developmentTransmission-blocking vaccine

Identifiers

PMID27038925
PMCPMC4818878
OpenAlexW2324629828

What OpenQuestion holds

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LicenceCC BY
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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.