@article{2cc80fc8636c4ad488cbdb99b7ecff70,
title = "RTS,S/AS01 malaria vaccine mismatch observed among Plasmodium falciparum isolates from southern and central Africa and globally",
abstract = "The RTS,S/AS01 malaria vaccine encompasses the central repeats and C-terminal of Plasmodium falciparum circumsporozoite protein (PfCSP). Although no Phase II clinical trial studies observed evidence of strain-specific immunity, recent studies show a decrease in vaccine efficacy against non-vaccine strain parasites. In light of goals to reduce malaria morbidity, anticipating the effectiveness of RTS,S/AS01 is critical to planning widespread vaccine introduction. We deep sequenced C-terminal Pfcsp from 77 individuals living along the international border in Luapula Province, Zambia and Haut-Katanga Province, the Democratic Republic of the Congo (DRC) and compared translated amino acid haplotypes to the 3D7 vaccine strain. Only 5.2% of the 193 PfCSP sequences from the Zambia-DRC border region matched 3D7 at all 84 amino acids. To further contextualize the genetic diversity sampled in this study with global PfCSP diversity, we analyzed an additional 3,809 Pfcsp sequences from the Pf3k database and constructed a haplotype network representing 15 countries from Africa and Asia. The diversity observed in our samples was similar to the diversity observed in the global haplotype network. These observations underscore the need for additional research assessing genetic diversity in P. falciparum and the impact of PfCSP diversity on RTS,S/AS01 efficacy.",
author = "Pringle, {Julia C.} and Giovanna Carpi and Jacob Almagro-Garcia and Zhu, {Sha Joe} and Tamaki Kobayashi and Modest Mulenga and Thierry Bobanga and Mike Chaponda and Moss, {William J.} and Norris, {Douglas E.}",
note = "Funding Information: We would like to thank the Southern and Central Africa International Centers of Excellence in Malaria Research (ICEMR) contributors and collaborators as well as the study participants and the communities of Nchelenge, Zambia and Haut-Katanga, DRC. This research is supported financially by The Molecular and Cellular Basis of Infectious Diseases (MCBID)T32 Training Grant (5T32AI007417-22) to JCP in the Department of Molecular Microbiology and Immunology (MMI) at the Johns Hopkins Bloomberg School of Public Health (JHSPH), the Bloomberg Philanthropies, a post-doctoral fellowship award to GC from the Johns Hopkins Malaria Research Institute (JHMRI), and the NIH-funded Southern and Central Africa International Centers of Excellence in Malaria Research (ICEMR) 2U19AI089680. SJZ is funded by the Wellcome Trust grant (100956/Z/13/Z) to Gil McVean. Funding Information: This research is supported financially by The Molecular and Cellular Basis of Infectious Diseases (MCBID)T32 Training Grant (5T32AI007417-22) to JCP in the Department of Molecular Microbiology and Immunology (MMI) at the Johns Hopkins Bloomberg School of Public Health (JHSPH), the Bloomberg Philanthropies, a post-doctoral fellowship award to GC from the Johns Hopkins Malaria Research Institute (JHMRI), and the NIH-funded Southern and Central Africa International Centers of Excellence in Malaria Research (ICEMR) 2U19AI089680. SJZ is funded by the Wellcome Trust grant (100956/Z/13/Z) to Gil McVean Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-24585-8",
language = "English (US)",
volume = "8",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}