A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273440 | PMC |
| http://dx.doi.org/10.7554/eLife.03582 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Type IV collagen derived non-collagenous domain α6 (IV) NC1 and its derivative fragments inhibit endothelial cell proliferation and attenuates chorioallantoic membrane angiogenesis.
Cytotechnology
April 2025
Department of Genetics, Osmania University, Hyderabad, Telangana State India.
Targeting tumor angiogenesis with safe endogenous protein inhibitors is a promising therapeutic approach despite the plethora of the first line of emerging chemotherapeutic drugs. The extracellular matrix network in the blood vessel basement membrane and growth factors released from endothelial and tumor cells promote the neovascularization which supports the tumor growth. Contrastingly, small cleaved cryptic fragments of the C-terminal non collagenous domains of the same basement membrane display antiangiogenic effect.
View Article and Find Full Text PDFInsulin Resistance Mediates the Association Between Vitamin D and Non-Alcoholic Fatty Liver Disease.
Int J Prev Med
December 2024
Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Affiliated Hospital of Southeast University, Xuzhou Clinical School of Nanjing Medical University, Xuzhou, Jiangsu, China.
Background: Vitamin D (VD) deficiency and insulin resistance (IR) increase the risk of non-alcoholic fatty liver disease (NAFLD), but few studies have explored the potential mechanisms by which IR mediates the association between VD and the pathogenesis of NAFLD at the genetic level using publicly available databases.
Methods: This is a cross-sectional study, and we utilized the National Health and Nutrition Examination Survey (NHANES) dataset, as well as data from GSE200765 obtained from the Gene Expression Omnibus (GEO) website. A total of 723 individuals who had completed liver ultrasound examination and the detection of VD levels were included in the final analysis.
Synaptotagmin-1 attenuates myocardial programmed necrosis and ischemia/reperfusion injury through the mitochondrial pathway.
Cell Death Dis
January 2025
Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, School of Basic Medicine, Shanxi Medical University, Taiyuan, China.
Programmed necrosis/necroptosis greatly contributes to the pathogenesis of cardiac disorders including myocardial infarction, ischemia/reperfusion (I/R) injury and heart failure. However, the fundamental mechanism underlying myocardial necroptosis, especially the mitochondria-dependent death pathway, is poorly understood. Synaptotagmin-1 (Syt1), a Ca sensor, is originally identified in nervous system and mediates synchronous neurotransmitter release.
View Article and Find Full Text PDFIdentification and regulation of a novel leptin receptor-linked enhancer during zebrafish ventricle regeneration.
Life Sci
January 2025
TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China. Electronic address:
Aims: Vertebrates vary greatly in their abilities to regenerate injured hearts. Zebrafish possess a remarkable capacity for cardiac regeneration, making them an excellent model for regeneration research. Recent studies have reported the activation and underlying regulatory mechanisms of leptin b (lepb) and the leptin b-linked enhancer (LEN) in injured hearts.
View Article and Find Full Text PDFLong-term exposure to fine particulate matter components with obesity in children and adolescents in China: The age-sex disparities and key effect modifiers.
Ecotoxicol Environ Saf
January 2025
Department of Endocrinology, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China. Electronic address:
Long-term fine particulate matter (PM) exposure was associated with childhood obesity. However, the key PM components and whether PM effect may vary by obesity type, growth stage, sex, and individual/family characteristics have yet been examined. In this study, we investigated 213,907 Chinese children and adolescents aged 3-18 years in 2017-2019.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!