PMID- 36841398 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20230505 IS - 1567-7257 (Electronic) IS - 1567-1348 (Linking) VI - 110 DP - 2023 Jun TI - Genetic variations of Plasmodium falciparum circumsporozoite protein and the impact on interactions with human immunoproteins and malaria vaccine efficacy. PG - 105418 LID - S1567-1348(23)00016-3 [pii] LID - 10.1016/j.meegid.2023.105418 [doi] AB - 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. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Dieng, Cheikh Cambel AU - Dieng CC AD - Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: cdieng@uncc.edu. FAU - Ford, Colby T AU - Ford CT AD - Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA; School of Data Science, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: colby.ford@uncc.edu. FAU - Lerch, Anita AU - Lerch A AD - Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA. FAU - Doniou, Dickson AU - Doniou D AD - Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana. FAU - Vegesna, Kovidh AU - Vegesna K AD - Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA. FAU - Janies, Daniel AU - Janies D AD - Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA. FAU - Cui, Liwang AU - Cui L AD - Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. FAU - Amoah, Linda AU - Amoah L AD - Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana; West Africa Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana. FAU - Afrane, Yaw AU - Afrane Y AD - Department of Microbiology, University of Ghana Medical School, University of Ghana, Accra, Ghana. FAU - Lo, Eugenia AU - Lo E AD - Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA; School of Data Science, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: eugenia.lo@uncc.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230224 PL - Netherlands TA - Infect Genet Evol JT - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases JID - 101084138 RN - 0 (Malaria Vaccines) RN - 0 (Protozoan Proteins) RN - 0 (Immunoproteins) RN - 0 (Histocompatibility Antigens Class II) SB - IM MH - Child MH - Humans MH - *Malaria Vaccines/genetics MH - Plasmodium falciparum MH - Ghana/epidemiology MH - Vaccine Efficacy MH - *Malaria MH - *Malaria, Falciparum/epidemiology/prevention & control MH - Protozoan Proteins MH - Immunoproteins/genetics/metabolism MH - Histocompatibility Antigens Class II/genetics MH - Genetic Variation OTO - NOTNLM OT - Binding interactions OT - Circumsporozoite protein OT - Malaria vaccine OT - Multiplicity of infection OT - Plasmodium falciparum OT - RTS,S-induced immunity COIS- Declaration of Competing Interest The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/02/25 19:30 PHST- 2023/01/03 00:00 [received] PHST- 2023/02/17 00:00 [revised] PHST- 2023/02/20 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/02/25 19:30 [entrez] AID - S1567-1348(23)00016-3 [pii] AID - 10.1016/j.meegid.2023.105418 [doi] PST - ppublish SO - Infect Genet Evol. 2023 Jun;110:105418. doi: 10.1016/j.meegid.2023.105418. Epub 2023 Feb 24.