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Identifying malaria vaccine candidate antigens using genetic linkage analyses

Research Project

Project/Area Number 19K07526
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49040:Parasitology-related
Research InstitutionEhime University (2020-2021)
Nagasaki University (2019)

Principal Investigator

Culleton Richard  愛媛大学, プロテオサイエンスセンター, 教授 (10503782)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsMalaria / Genetics / Genomics / malaria / P. vinckei / vaccine / LGS / RMP / Plasmodium vinckei / WGS / genetics / crossing / Vaccine / Genetic linkage analysis
Outline of Research at the Start

In order to design new vaccines for malaria, proteins that play crucial roles in inducing protective host immunity must be identified. I propose to identify targets of host immunity using Linkage Group Selection (LGS) and the experimental rodent malaria parasite system, Plasmodium vinckei. I propose systematically test the ability of combinations of strains of P. vinckei to induce strain specific immunity in mice, then apply LGS to attempt to identify the genes that encode protective antigens.

Outline of Final Research Achievements

We have generated a comprehensive genetic resource for P. vinckei comprising of five reference-quality genomes, one for each of its subspecies, blood-stage RNA sequencing data for five P. vinckei isolates, and genotypes and growth phenotypes for ten isolates. Additionally, we sequenced seven isolates of the RMP species Plasmodium chabaudi and Plasmodium yoelii, thus extending genotypic information for four additional subspecies enabling a re-evaluation of the genotypic diversity and evolutionary history of RMPs. The subspecies from the highland forests of Katanga, P. v. vinckei, has a uniquely smaller genome, a reduced multigene family repertoire and is also amenable to transfection making it an ideal parasite for reverse genetics. We also show that P. vinckei parasites are amenable to genetic crosses.

Academic Significance and Societal Importance of the Research Achievements

Plasmodium vinckei isolates display a large degree of phenotypic and genotypic diversity and could serve as a resource to study parasite virulence and immunogenicity. Amenability to genetic crossing and transfection make them also suitable for classical and functional genetics to study malaria.

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 4 results)

  • [Journal Article] High prevalence of Plasmodium malariae and Plasmodium ovale in co-infections with Plasmodium falciparum in asymptomatic malaria parasite carriers in southwestern Nigeria2022

    • Author(s)
      Abdulraheem Muhydeen Abiodun、Ernest Medard、Ugwuanyi Ifeoma、Abkallo Hussein M.、Nishikawa Saori、Adeleke Mofeyisade、Orimadegun Adebola E.、Culleton Richard
    • Journal Title

      International Journal for Parasitology

      Volume: 52 Issue: 1 Pages: 23-33

    • DOI

      10.1016/j.ijpara.2021.06.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Plasmodium vinckei genomes provide insights into the pan-genome and evolution of rodent malaria parasites2021

    • Author(s)
      Ramaprasad Abhinay、Klaus Severina、Douvropoulou Olga、Culleton Richard、Pain Arnab
    • Journal Title

      BMC Biology

      Volume: 19 Issue: 1

    • DOI

      10.1186/s12915-021-00995-5

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevalence of Plasmodium falciparum isolates lacking the histidine rich protein 2 gene among symptomatic malaria patients in Kwilu Province of the Democratic Republic of Congo2021

    • Author(s)
      Munyeku Yannick Bazitama、Musaka Alain Abera、Ernest Medard、Smith Chris、Mansiangi Paul Mankadi、Culleton Richard
    • Journal Title

      Infectious Diseases of Poverty

      Volume: 10 Issue: 1

    • DOI

      10.1186/s40249-021-00860-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms2020

    • Author(s)
      Subudhi Amit K.、O’Donnell Aidan J.、Ramaprasad Abhinay、Abkallo Hussein M.、Kaushik Abhinav、Ansari Hifzur R.、Abdel-Haleem Alyaa M.、Ben Rached Fathia、Kaneko Osamu、Culleton Richard、Reece Sarah E.、Pain Arnab
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41467-020-16593-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Consequences of Mixed-Species Malaria Parasite Co-Infections in Mice and Mosquitoes for Disease Severity, Parasite Fitness, and Transmission Success2020

    • Author(s)
      Tang Jianxia、Templeton Thomas J.、Cao Jun、Culleton Richard
    • Journal Title

      Frontiers in Immunology

      Volume: 10

    • DOI

      10.3389/fimmu.2019.03072

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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