Expression of full-length Plasmodium falciparum P48/45 in P. berghei blood stages: A method to express and evaluate vaccine antigens.

Autor: Othman AS; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands; Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Terengganu, Malaysia., Lin JW; Division of Pediatric Infectious Diseases, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaboration Innovation Center, Chengdu, China., Franke-Fayard BM; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Kroeze H; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., van Pul FJA; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Chevalley-Maurel S; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Ramesar J; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Marin-Mogollon C; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Jore MM; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Morin MJ; PATH's Malaria Vaccine Initiative, Washington DC, USA., Long CA; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA., Sauerwein R; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Birkett A; PATH's Malaria Vaccine Initiative, Washington DC, USA., Miura K; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA., Janse CJ; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Khan SM; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. Electronic address: S.M.Khan@lumc.nl.
Jazyk: angličtina
Zdroj: Molecular and biochemical parasitology [Mol Biochem Parasitol] 2018 Sep; Vol. 224, pp. 44-49. Date of Electronic Publication: 2018 Jul 24.
DOI: 10.1016/j.molbiopara.2018.07.009
Abstrakt: The transmission-blocking vaccine candidate Pfs48/45 from the human malaria parasite Plasmodium falciparum is known to be difficult to express in heterologous systems, either as full-length protein or as correctly folded protein fragments that retain conformational epitopes. In this study we express full-length Pfs48/45 in the rodent parasite P. berghei. Pfs48/45 is expressed as a transgene under control of the strong P. berghei schizont-specific msp1 gene promoter (Pfs48/45@PbMSP1). Pfs48/45@PbMSP1 schizont-infected red blood cells produced full-length Pfs48/45 and the structural integrity of Pfs48/45 was confirmed using a panel of conformation-specific monoclonal antibodies that bind to different Pfs48/45 epitopes. Sera from mice immunized with transgenic Pfs48/45@PbMSP1 schizonts showed strong transmission-reducing activity in mosquitoes infected with P. falciparum using standard membrane feeding. These results demonstrate that transgenic rodent malaria parasites expressing human malaria antigens may be used as means to evaluate immunogenicity and functionality of difficult to express malaria vaccine candidate antigens.
(Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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