دورية أكاديمية
أعرض في EDS

Monoclonal antibodies block transmission of genetically diverse Plasmodium falciparum strains to mosquitoes.

التفاصيل البيبلوغرافية
العنوان: Monoclonal antibodies block transmission of genetically diverse Plasmodium falciparum strains to mosquitoes.
المؤلفون: de Jong RM; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Meerstein-Kessel L; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.; Center for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands., Da DF; Institut de Recherche en Sciences de la Santé, Direction Régionale, Bobo Dioulasso, Burkina Faso., Nsango S; Malaria Research Laboratory, OCEAC, Yaoundé, Cameroon.; Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon., Challenger JD; Medical Research Council Centre for Global Infections Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK., van de Vegte-Bolmer M; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., van Gemert GJ; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Duarte E; EPPIcenter Research Program, Division of HIV, ID, and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA., Teyssier N; EPPIcenter Research Program, Division of HIV, ID, and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA., Sauerwein RW; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.; TropIQ Health Sciences, Nijmegen, Netherlands., Churcher TS; Medical Research Council Centre for Global Infections Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK., Dabire RK; Institut de Recherche en Sciences de la Santé, Direction Régionale, Bobo Dioulasso, Burkina Faso., Morlais I; Malaria Research Laboratory, OCEAC, Yaoundé, Cameroon.; MIVEGEC, Université Montpellier, IRD, CNRS, Montpellier, France., Locke E; PATH's Malaria Vaccine Initiative, Washington, DC, USA., Huynen MA; Center for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands., Bousema T; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. Teun.bousema@radboudumc.nl., Jore MM; Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. Matthijs.jore@radboudumc.nl.
المصدر: NPJ vaccines [NPJ Vaccines] 2021 Aug 12; Vol. 6 (1), pp. 101. Date of Electronic Publication: 2021 Aug 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Nature in partnership with the Sealy Center for Vaccine Development Country of Publication: England NLM ID: 101699863 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-0105 (Electronic) Linking ISSN: 20590105 NLM ISO Abbreviation: NPJ Vaccines Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Springer Nature in partnership with the Sealy Center for Vaccine Development, [2016]-
مستخلص: Malaria parasite transmission to mosquitoes relies on the uptake of sexual stage parasites during a blood meal and subsequent formation of oocysts on the mosquito midgut wall. Transmission-blocking vaccines (TBVs) and monoclonal antibodies (mAbs) target sexual stage antigens to interrupt human-to-mosquito transmission and may form important tools for malaria elimination. Although most epitopes of these antigens are considered highly conserved, little is known about the impact of natural genetic diversity on the functional activity of transmission-blocking antibodies. Here we measured the efficacy of three mAbs against leading TBV candidates (Pfs48/45, Pfs25 and Pfs230) in transmission assays with parasites from naturally infected donors compared to their efficacy against the strain they were raised against (NF54). Transmission-reducing activity (TRA) was measured as reduction in mean oocyst intensity. mAb 45.1 (α-Pfs48/45) and mAb 4B7 (α-Pfs25) reduced transmission of field parasites from almost all donors with IC 80 values similar to NF54. Sequencing of oocysts that survived high mAb concentrations did not suggest enrichment of escape genotypes. mAb 2A2 (α-Pfs230) only reduced transmission of parasites from a minority of the donors, suggesting that it targets a non-conserved epitope. Using six laboratory-adapted strains, we revealed that mutations in one Pfs230 domain correlate with mAb gamete surface binding and functional TRA. Our findings demonstrate that, despite the conserved nature of sexual stage antigens, minor sequence variation can significantly impact the efficacy of transmission-blocking mAbs. Since mAb 45.1 shows high potency against genetically diverse strains, our findings support its further clinical development and may inform Pfs48/45 vaccine design.
(© 2021. The Author(s).)
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معلومات مُعتمدة: MR/R015600/1 RCUK | Medical Research Council (MRC); MR/R015600/1 RCUK | Medical Research Council (MRC); 192.061 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
تواريخ الأحداث: Date Created: 20210813 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC8361195
DOI: 10.1038/s41541-021-00366-9
PMID: 34385463
قاعدة البيانات: MEDLINE
الوصف
تدمد:2059-0105
DOI:10.1038/s41541-021-00366-9