Evidence map›Paper›PMID 31915075›Full record

ArticleGenome medicine2020

Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential.

Kara A Moser, Elliott F Drábek, Ankit Dwivedi, Emily M Stucke, Jonathan Crabtree, Antoine Dara, Zalak Shah, Matthew Adams, Tao Li, Priscila T Rodrigues and 24 more

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
10.8field-weighted citation impact, top 1% 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

54 citing papers in PubMed, 86 citations in OpenAlex.

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  13. Malaria: past, present, and future.Signal transduction and targeted therapy · 2025
    Review
  14. Diamonds in the rif: Alignment-free comparative genomics analysis reveals strain-transcendent Plasmodium falciparum antigens amidst extensive genetic diversity.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2025
    Article
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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

34 authors at 8 institutions in 4 countries.

Kara A MoserInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Elliott F DrábekInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Ankit DwivediInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Emily M StuckeCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Jonathan CrabtreeInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Antoine DaraCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Zalak ShahCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Matthew AdamsCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Tao LiSanaria, Inc., Rockville, MD, 20850, USA.
Priscila T RodriguesDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Sergey KorenGenome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, Bethesda, MD, 20892, USA.
Adam M PhillippyGenome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, Bethesda, MD, 20892, USA.
James B MunroInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Amed OuattaraCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Benjamin C SparklinInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Julie C Dunning HotoppInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Kirsten E LykeCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Lisa SadzewiczInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Luke J TallonInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Michele D SpringDepartment of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Krisada JongsakulDepartment of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Chanthap LonDepartment of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
David L SaundersDepartment of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Marcelo U FerreiraDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Myaing M NyuntCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Miriam K LauferCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Mark A TravassosCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Robert W SauerweinDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands.
Shannon Takala-HarrisonCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Claire M FraserInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
B Kim Lee SimSanaria, Inc., Rockville, MD, 20850, USA.
Stephen L HoffmanSanaria, Inc., Rockville, MD, 20850, USA.
Christopher V PloweCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Joana C SilvaInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. jcsilva@som.umaryland.edu.ORCID 0000-0001-6502-7026
University of Maryland, Baltimore · USArmed Forces Research Institute of Medical Science · THSanaria · USNational Human Genome Research Institute · USUniversidade de São Paulo · BRRadboud University Nijmegen · NLUnited States Army Medical Research and Development Command · USUniversity of North Carolina at Chapel Hill · US

Funding

Technology CoreU19AI110820 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI WHITE, OWEN R · 2014 to 2023
$36.5M
The role of monocytes in the pathology of severe malaria.U19AI089683 · NIAID · MICHIGAN STATE UNIVERSITY · PI MATHANGA, DON P, TAYLOR, TERRIE ELLEN · 2010 to 2023
$21.4M
Sugar-feeding behavior of the malaria vector Nyssorhynchus darlingi and development of effective attractive toxic sugar baits (ATSB) to increase intervention success in PeruU19AI089681 · NIAID · YALE UNIVERSITY · PI CASTRO, MARCIA C. · 2010 to 2023
$20.1M
EXPAND PARTICIPATION BY MINORITIES IN BIOMEDICAL SCIENCER25GM055036 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SUMMERS, MICHAEL FINLEY · 1996 to 2021
$16.9M
Single-molecule sequence assembly and analysisZIAHG200398 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI PHILLIPPY, ADAM · 2016 to 2025
$15.9M
Plasmodium Falciparum Whole Sporozoite Malaria VaccineR44AI055229 · NIAID · SANARIA, INC. · PI HOFFMAN, STEPHEN LEV · 2005 to 2015
$10.0M
Universal Attenuated Sporozoite Vaccine and Challenge SystemR44AI058375 · NIAID · SANARIA, INC. · PI HOFFMAN, STEPHEN LEV · 2006 to 2018
$9.9M
Genome-wide sieve analysis and immunological validation to identify targets of protective efficacy in field trials of a whole-organism malaria vaccineR01AI141900 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI CARNEIRO DA SILVA, JOANA · 2019 to 2023
$3.9M
Identification and validation of molecular markers of piperaquine resistanceR01AI125579 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI HARRISON, SHANNON TAKALA · 2017 to 2021
$1.6M
Designing a diversity-covering multiantigen multi-strain vaccineK01HL140285 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI OUATTARA, AMED · 2019 to 2023
$712k
Identification of parasite erythrocyte membrane antigens specific to cerebral malaria and severe malarial anemia pathogenesisF31HL147471 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI STUCKE, EMILY MARIE · 2019 to 2021
$83k
Howard Hughes Medical InstituteIntramural NIH HHS ZIA HG200398NHGRI NIH HHS 1ZIAHG200398NHLBI NIH HHS F31 HL147471NHLBI NIH HHS K01 HL140285NIAID NIH HHS R01 AI125579NIAID NIH HHS R01 AI141900NIAID NIH HHS R44 AI055229NIAID NIH HHS R44 AI058375NIAID NIH HHS U19 AI089681NIAID NIH HHS U19 AI089683NIAID NIH HHS U19 AI110820NIGMS NIH HHS R25 GM055036
6 · The paper itself

Abstract

backgroundPlasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions.

methodsWhole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia.

resultsWhile few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8

conclusionsThese results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI.

Indexed as

Immunogenicity, VaccinePolymorphism, GeneticCD8-Positive T-LymphocytesClinical Trials as TopicGenome, ProtozoanHumansMalaria VaccinesPlasmodium falciparumMalaria VaccinesGenome assemblyMalariaP. falciparumPfSPZ vaccineWhole-sporozoite vaccine

Identifiers

PMID31915075
PMCPMC6950926
OpenAlexW3004046469

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.