Journal article
Genetic variations of Plasmodium falciparum circumsporozoite protein and the impact on interactions with human immunoproteins and malaria vaccine efficacy
Infection, genetics and evolution, v 110, 105418
01 Jun 2023
PMID: 36841398
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In October 2021, the world's first malaria vaccine RTS,S was endorsed by WHO for broad use in children, despite its low efficacy. This study examined polyclonal infections and the associations of parasite genetic variations with binding affinity to human leukocyte antigen (HLA). Multiplicity of infection was determined by amplicon deep sequencing of PfMSP1. Genetic variations in PfCSP were examined across 88 samples from Ghana and analyzed together with 1655 PfCSP sequences from other African and non-African isolates. Binding interactions of PfCSP peptide variants and HLA were predicted using NetChop and HADDOCK. High polyclonality was detected among infections, with each infection harboring multiple non-3D7 PfCSP variants. Twenty-seven PfCSP haplotypes were detected in the Ghanaian samples, and they broadly represented PfCSP diversity across Africa. The number of genetic differences between 3D7 and non-3D7 PfCSP variants does not influence binding to HLA. However, CSP peptide length after proteolytic degradation significantly affects its molecular weight and binding affinity to HLA. Despite the high diversity of HLA, the majority of the HLAI and II alleles interacted/bound with all Ghana CSP peptides. Multiple non-3D7 strains among P. falciparum infections could impact the effectiveness of RTS,S. Longer peptides of the Th2R/Th3R CSP regions should be considered in future versions of RTS,S.
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Details
- Title
- Genetic variations of Plasmodium falciparum circumsporozoite protein and the impact on interactions with human immunoproteins and malaria vaccine efficacy
- Creators
- Cheikh Cambel Dieng - University of North Carolina at CharlotteColby T. Ford - University of North Carolina at CharlotteAnita Lerch - University of Notre DameDickson Doniou - University of GhanaKovidh Vegesna - University of North Carolina at CharlotteDaniel Janies - University of North Carolina at CharlotteLiwang Cui - University of South FloridaLinda Amoah - University of GhanaYaw Afrane - University of GhanaEugenia Lo - University of North Carolina at Charlotte
- Publication Details
- Infection, genetics and evolution, v 110, 105418
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- University of North Carolina Charlotte Faculty Research Grant at The University of North Carolina Charlotte
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001042596000001
- Scopus ID
- 2-s2.0-85149302280
- Other Identifier
- 991022192515604721
UN Sustainable Development Goals (SDGs)
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Source: SDGs in the Output
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Infectious Diseases