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| http://dx.doi.org/10.1016/j.jinf.2022.10.026 | DOI Listing |
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Single immunization with genetically attenuated Pf∆mei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial.
Nat Med
January 2025
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Malaria vaccines consisting of metabolically active Plasmodium falciparum (Pf) sporozoites can offer improved protection compared with currently deployed subunit vaccines. In a previous study, we demonstrated the superior protective efficacy of a three-dose regimen of late-arresting genetically attenuated parasites administered by mosquito bite (GA2-MB) compared with early-arresting counterparts (GA1-MB) against a homologous controlled human malaria infection. Encouraged by these results, we explored the potency of a single GA2-MB immunization in a placebo-controlled randomized trial.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The University of Queensland, Brisbane, QLD, Australia.
Ageing changes the adult brain at the molecular, cellular and functional levels, driving regenerative decline, inflammation, cognitive impairments and susceptibility to dementia-related neurodegenerative disorders, such as Alzheimer's disease (AD). There is overwhelming evidence that regular physical exercise can counteract cognitive decline in both healthy ageing and in neurodegenerative conditions such as AD, with exerkines, the circulating humoral factors that are secreted into the blood stream in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear.
View Article and Find Full Text PDFProteomic characterization of molecular mechanisms of paraquat-induced lung injury in a mouse model.
Respir Res
January 2025
Emergency Department, The First Hospital of China Medical University, No.155 North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, China.
Background: We sought to explore the molecular mechanisms underpinning acute lung injury (ALI) caused by poisoning with paraquat (PQ).
Methods: Selection mice were intraperitoneally injected with PQ at 40 mg/kg, whereas controls were injected with sterile saline. On days 2, 7, and 14 after administration, mice were anesthetized and sacrificed, and lung tissue was removed.
Rational engineering of minimally immunogenic nucleases for gene therapy.
Nat Commun
January 2025
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a.
View Article and Find Full Text PDFImmune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia.
Nat Commun
January 2025
Department of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube.
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