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

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About: Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential
Creator	Lon, Chanthap Saunders, David Li, Tao Adams, Matthew Kim, B Sauerwein, Robert Fraser, Claire Hoffman, Stephen Lyke, Kirsten Ferreira, Marcelo Phillippy, Adam Laufer, Miriam Munro, James Nyunt, Myaing Ouattara, Amed Plowe, Christopher Silva, Joana Spring, Michele Takala-Harrison, Shannon Travassos, Mark Koren, Sergey Moser, Kara Shah, Zalak Stucke, Emily Crabtree, Jonathan Dara, Antoine Drábek, Elliott Dunning Hotopp, Julie Dwivedi, Ankit Jongsakul, Krisada Rodrigues, Priscila Sadzewicz, Lisa Sparklin, Benjamin Tallon, Luke Sim, Lee
Source	PMC
abstract	BACKGROUND: Plasmodium 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. METHODS: Whole 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. RESULTS: While 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(+) T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. CONCLUSIONS: These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-019-0708-9) contains supplementary material, which is available to authorized users.
has issue date	2020-01-08(xsd:dateTime)
bibo:doi	10.1186/s13073-019-0708-9
bibo:pmid	31915075
has license	cc-by
sha1sum (hex)	b3ecad2c4a8fdb0a79eaeb8b9529995f9e9b0f0e
schema:url	https://doi.org/10.1186/s13073-019-0708-9
resource representing a document's title	Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential
has PubMed Central identifier	PMC6950926
has PubMed identifier	31915075
schema:publication	Genome Med
resource representing a document's body	covid:b3ecad2c4a8fdb0a79eaeb8b9529995f9e9b0f0e#body_text
is schema:about of	named entity 'clone' named entity 'CHMI' named entity 'repositories' named entity 'immunogenic' covid:arg/b3ecad2c4a8fdb0a79eaeb8b9529995f9e9b0f0e named entity 'test case' named entity 'epitope' named entity 'Cambodia' named entity 'malaria' named entity 'allele' named entity 'contigs' named entity '10.5' named entity 'genomes' named entity 'Illumina HiSeq 2500' named entity 'genome' named entity '2.1' named entity 'genome' named entity 'erythrocytic' named entity 'HLA' named entity 'antigen' named entity 'SNP' named entity 'premature stop codon' named entity 'epitope' named entity 'high-quality' named entity 'P. falciparum' named entity 'SNPs' named entity 'complex life cycles' named entity 'infection' named entity 'proline' named entity 'spreadsheet' named entity 'hepatocytes' named entity 'Beckman Coulter' named entity 'exon' named entity 'RBCs' named entity 'Kenya' named entity 'locus' named entity 'epitopes' named entity 'UPS' named entity 'genetic diversity' named entity 'CHMI' named entity 'gene expression' named entity 'antigens' named entity 'Burkina Faso' named entity 'CHMI' named entity 'antigens' named entity 'homologous' named entity 'drug resistance'

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