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Community Series in Vaccines and approaches that target trained immunity in COVID-19: Immunological mechanisms of action and delivery: Volume II

2024 This is a first of its kind univversal covid 19 vaccine that would allow for a one time shot that is good for current versions of the virus and future versions aswell.

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.

According to the World Health Organization, as of March 15, 2024, over 774 million COVID-19 cases and almost 7 million related deaths had been reported globally. A total of 13.59 billion doses of COVID-19 vaccines have been reportedly administered globally, leading to a vaccination rate of 69.7%. At present, at least 24 types of COVID-19 vaccines have been authorized for emergency use in various countries. According to the list of global COVID-19 candidate vaccines published on the WHO website, a total of 183 candidate vaccines are in clinical development and 199 candidate vaccines are in the preclinical evaluation stage as of April 8, 2023. Recombinant protein subunit vaccines account for the greatest proportion of vaccines in clinical development (59 vaccines, 32%), followed by RNA vaccines (43 vaccines, 24%).

Exploring the role of apolipoprotein ε4 in progressive myoclonic epilepsy type 1

“Despite greater white matter degeneration and reduced cortical thickness, APOE ε4 carriers exhibited preserved deep brain volumes and better self-reported well-being. This study highlights the complex interplay between genetic factors and neurodegenerative processes. Our future research aims to provide more natural history data of EPM1 and correlate long-term phenotypic data with additional geno-phenotypic analyses.”

Read this original article from Epileptic Disorders at doi.org/10.1002/epd2.70112.

Objective Progressive myoclonic epilepsy type 1 (EPM1) is a neurodegenerative disease caused by biallelic variants in the cystatin B (CSTB) gene. Despite a progressive course, phenotype severity varies among patients, even within families. We studied the potential role of APOE ε4 in modifying phenotypic diversity in EPM1, given its established association with neurodegeneration, particularly in Alzheimer’s disease.

B cells join T cells to drive sight-threatening arthritis in children

A team led by UCL researchers with Great Ormond Street Hospital (GOSH) and Moorfields Eye Hospital, found B cells—alongside T cells—play a key role in arthritis-related eye disease (JIA uveitis), a condition that can cause long-term vision loss in children. The study challenges how the disease has been previously understood, and could open the door to new treatments that help protect children’s sight.

Juvenile idiopathic arthritis (JIA) is the most common form of arthritis in children under the age of 16, affecting around one in every 1,000 children in the UK. Approximately 30% of patients with JIA also develop uveitis—an inflammatory condition of the eye that is potentially sight-threatening.

Although some treatments are available today for the condition, up to a third of affected children still experience some degree of permanent vision loss by the time they reach adulthood.

An off-the-shelf immunotherapy for targeting solid tumors: Ready-to-use CAR-NKT cells show promise

A UCLA research team has identified the best design for a promising new type of immunotherapy that could be mass-produced to treat multiple solid tumors. The study focused on engineered invariant natural killer T cells, or NKT cells—powerful immune cells with a unique ability to infiltrate solid tumors—and systematically compared four targeting systems, called chimeric antigen receptors, or CARs, that direct these cells to attack cancer.

The study was published in the journal Blood Immunology & Cellular Therapy.

CAR-T cell therapies have revolutionized treatment for certain blood cancers like leukemia and lymphoma, but these successes haven’t extended to solid tumors, which make up the vast majority of cancers. Solid tumors build dense protective barriers that block therapeutic cells from reaching the cancer and display varied targets that allow cancer cells to escape detection.

Distinct Mutations in the Same Gene Drive Cancer Differently

Scientists mapped every possible mutation in a key genetic hotspot, revealing how distinct mutations drive tumor growth differently, which could influence anticancer therapy success.

Read more.

Mapping diverse mutations within a cancer hotspot revealed that distinct variants drive tumor growth to different extents, which could guide anticancer therapies.

A simple blood test could change how Alzheimer’s is diagnosed

A blood test, combined with an ultrathin material derived from graphite, could significantly advance efforts to detect Alzheimer’s disease at its very earliest stage, even before symptoms appear.

Alzheimer’s disease is the most common form of dementia. For millions of Europeans—and the health services that care for them—it is a ticking time bomb, with still no cure. But EU researchers are developing a simple tool to enable much earlier detection, potentially decades before symptoms appear.

Early detection matters because treatment is most effective when started as soon as possible. This gives people a better chance to slow the progression of the disease and plan for the future. Today, around 7 million people in Europe live with Alzheimer’s, a number expected to double by 2030, according to the European Brain Council.

Abstract: It’s about TIME (tumor immune microenvironment) for BreastCancer

Here, Carlos L. Arteaga & team analyze patient biopsies, finding CD8+ T cells in the TIME promote resistance to estrogen suppression in HR+ breast cancer via CXCL11 and immune-related pathways:

The images: GeoMx-based immunofluorescence of breast tumor tissue obtained during estrogen deprivation therapy (letrozole) demonstrates increased immune cell infiltration in estrogen deprivation–resistant tumors (right) compared with sensitive tumors (left).

1UT Southwestern Simmons Comprehensive Cancer Center, Department of Internal Medicine, University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA.

2Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

3Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA.

Few studies report on urinary microbiota, especially in pediatric conditions

Here, Miguel Verbitsky & team analyze urine from 325 participants in the Randomized Intervention for Children with Vesicoureteral Reflux study (RIVUR study), revealing genetic variations influence bacterial composition of urine in children with recurrent urinary infections and vesicoureteral reflux:

The image shows cytokeratin 5 and smooth muscle actin labeling after UTI in mouse bladder, which increases expression of Cxcl12 and Cxcr4.

3Department of Dermatology; and.

4Center for Precision Medicine and Genomics, Columbia University, New York, New York, USA.

5Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

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