Academic Journal
The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.
العنوان: | The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo. |
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المؤلفون: | Yevel Flores-Garcia, Lawrence T Wang, Minah Park, Beejan Asady, Azza H Idris, Neville K Kisalu, Christian Muñoz, Lais S Pereira, Joseph R Francica, Robert A Seder, Fidel Zavala |
المصدر: | PLoS Pathogens, Vol 17, Iss 11, p e1010042 (2021) |
بيانات النشر: | Public Library of Science (PLoS), 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
الوصف: | Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1553-7366 1553-7374 |
Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
DOI: | 10.1371/journal.ppat.1010042 |
URL الوصول: | https://doaj.org/article/4b2f0abc1d8945d0affa55beb09edf04 |
رقم الانضمام: | edsdoj.4b2f0abc1d8945d0affa55beb09edf04 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 15537366 15537374 |
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DOI: | 10.1371/journal.ppat.1010042 |