Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling antigen release, typically involving various approaches at the injection site. Yet, strategies for intracellular slow-release of antigens in vaccines are still unexplored. Our study showed that controlling the degradation of antigens in dendritic cells and slowing their transport from early endosomes to lysosomes markedly enhances both antigen-specific T-cell immune responses and germinal center B cell responses. This leads to the establishment of sustained humoral and cellular immunity in vivo imaging and flow cytometry indicated this method not only prolongs antigen retention at the injection site but also enhances antigen concentration in lymph nodes, surpassing traditional Aluminium (Alum) adjuvants. Additionally, we demonstrated that the slow antigen degradation induces stronger follicular helper T cell responses and increases proportions of long-lived plasma cells and memory B cells. Overall, these findings propose that controlling the speed of antigens transport in dendritic cells can significantly boost vaccine efficacy, offering an innovative avenue for developing highly immunogenic next-generation vaccines.
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http://dx.doi.org/10.1016/j.biopha.2024.117036 | DOI Listing |
Background: Alzheimer's disease (AD) is a devastating form of dementia, and its prevalence is rising as human lifespan increases. Our lab created the AD-BXD mouse model, which expresses AD mutations across a genetically diverse reference panel (BXD), to identify factors that confer resilience to cognitive decline in AD. This model mimics key characteristics of human AD including variation in age of onset and severity of cognitive decline.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Afe Babalola University, Ado-Ekiti (ABUAD), Ado-Ekiti, Ekiti state, Nigeria.
Background: The impact of probiotics as gut and immunological modulator in restoring gut microbial balance and immune cells expression have generated much attention in the health sector. Its inhibitory effect on bacterial translocation and associated neural inflammatory processes has been reported. However, there is scarcity of data on its neuroprotective impact against neuroinflammation-associated neurodegeneration and memory impairment.
View Article and Find Full Text PDFBackground: Understanding the fundamental differences between the human and pre-human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance.
Method: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP).
Background: A 73-year-old female with a 3 year history of Alzheimer's disease was treated within the protocol of The Alzheimer's Autism and Cognitive Impairment Stem Cell Treatment Study (ACIST), an IRB approved clinical study registered with clinicaltrials.gov NCT03724136.
Method: The procedure consists of bone marrow aspiration, cell separation using an FDA cleared class 2 device, and intravenous and intranasal administration of the stem cell fraction.
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