AI Article Synopsis
Article Abstract
It has been estimated that more than 390 million people are infected with Dengue virus every year; around 96 millions of these infections result in clinical pathologies. To date, there is only one licensed viral vector-based Dengue virus vaccine CYD-TDV approved for use in dengue endemic areas. While initially approved for administration independent of serostatus, the current guidance only recommends the use of this vaccine for seropositive individuals. Therefore, there is a critical need for investigating the influence of Dengue virus serostatus and immunological mechanisms that influence vaccine outcome. Here, we provide comprehensive evaluation of sero-status and host immune factors that correlate with robust immune responses to a Dengue virus vector based tetravalent vaccine (TV003) in a Phase II clinical cohort of human participants. We observed that sero-positive individuals demonstrate a much stronger immune response to the TV003 vaccine. Our multi-layered immune profiling revealed that sero-positive subjects have increased baseline/pre-vaccination frequencies of circulating T follicular helper (cTfh) cells and the Tfh related chemokine CXCL13/BLC. Importantly, this baseline/pre-vaccination cTfh profile correlated with the vaccinees' ability to launch neutralizing antibody response against all four sero-types of Dengue virus, an important endpoint for Dengue vaccine clinical trials. Overall, we provide novel insights into the favorable cTfh related immune status that persists in Dengue virus sero-positive individuals that correlate with their ability to mount robust vaccine specific immune responses. Such detailed interrogation of cTfh cell biology in the context of clinical vaccinology will help uncover mechanisms and targets for favorable immuno-modulatory agents.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809550 | PMC |
| http://dx.doi.org/10.1371/journal.ppat.1009903 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Predicting the infecting dengue serotype from antibody titre data using machine learning.
PLoS Comput Biol
December 2024
MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics, School of Public Health, Imperial College London, London, United Kingdom.
The development of a safe and efficacious vaccine that provides immunity against all four dengue virus serotypes is a priority, and a significant challenge for vaccine development has been defining and measuring serotype-specific outcomes and correlates of protection. The plaque reduction neutralisation test (PRNT) is the gold standard assay for measuring serotype-specific antibodies, but this test cannot differentiate homotypic and heterotypic antibodies and characterising the infection history is challenging. To address this, we present an analysis of pre- and post-infection antibody titres measured using the PRNT, collected from a prospective cohort of Thai children.
View Article and Find Full Text PDFRole of Vigilin and RACK1 in dengue virus- interactions.
mSphere
December 2024
Australian Infectious Disease Research Centre, School of Biological Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Vigilin is a large and evolutionary conserved RNA-binding protein (RBP), which can interact with RNA through its KH domain. Vigilin is, therefore, a multifunctional protein reported to be associated with RNA transport and metabolism, sterol metabolism, chromosome segregation, carcinogenesis, and heterochromatin-mediated gene silencing. The receptor for activated C kinase 1 (RACK1) is another highly conserved protein involved in many cellular pathways.
View Article and Find Full Text PDFSuccessful Management of Severe Dengue With Gastrointestinal Bleeding: A Case Report Highlighting Endoscopic Hemostasis.
Cureus
November 2024
Internal Medicine, Al Qassimi Hospital, Sharjah, ARE.
Dengue fever, caused by the dengue virus and transmitted by mosquitoes, poses a significant global health threat, particularly in tropical and subtropical regions. Severe cases can manifest as dengue hemorrhagic fever (DHF) or dengue shock syndrome, leading to complications such as plasma leakage, fluid accumulation, respiratory distress, severe bleeding, and organ impairment. Among these complications, gastrointestinal (GI) bleeding is particularly concerning due to its potential to rapidly deteriorate the patient's condition.
View Article and Find Full Text PDFDengue virus (DENV) is an increasingly important human pathogen, with already half of the globe's population living in environments with transmission potential. Since only a minority of cases are captured by direct detection methods (RT-PCR or antigen tests), serological assays play an important role in the diagnostic process. However, individual assays can suffer from low sensitivity and specificity and interpreting results from multiple assays remains challenging, particularly because interpretations from multiple assays may differ, creating uncertainty over how to generate finalized interpretations.
View Article and Find Full Text PDFThe climate emergency for rheumatologists: where do we stand?
Clin Rheumatol
December 2024
Department of Medicine, University of Otago, Wellington, New Zealand.
Climate change and pollution are a major existential threat. Healthcare contributes a noteworthy 4-6% to the total carbon footprint and 5-7% of the total greenhouse gas (GHG) emissions. Environmental pollution and modern lifestyles are also contributing to the increased prevalence of autoimmune and lifestyle-related rheumatic disease.
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!