Research Roundup: Another Promising COVID-19 Vaccine and More

Clinical Research

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

Another COVID-19 Vaccine Looks Promising

According to the World Health Organization, there are 70 vaccines being developed worldwide for COVID-19, with three already in human clinical trials. The furthest along is one by CanSino Biologics and the Beijing Institute of Biotechnology, which is in Phase II. The others are by U.S. companies, Inovio Pharmaceuticals and Moderna. Another institution, the University of Pittsburgh, also announced that in laboratory tests their COVID-19 vaccine, delivered via a fingertip-sized patch, showed positive results in laboratory mice, producing antibodies specific to SARS-CoV-2 at enough amounts to neutralize the virus. The research was published in EBioMedicine, published by The Lancet.

“We had previous experience on SARS-CoV in 2003 and MERS-COV in 2014,” said co-senior author Andrea Gambotta, associate professor of surgery at the Pitt School of Medicine. “These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We know exactly where to fight this new virus. That’s why it’s important to fund vaccine research. You never know where the next pandemic will come from.”

It uses a more traditional process than the mRNA one being used by Moderna. The virus is being called PittCOVacc, and uses laboratory-manufactured pieces of viral protein to build immunity. It’s a process similar to that used in seasonal flu shots. They also leveraged a new technique to deliver the drug, called a microneedle array, to increase the potency of the vaccine. The fingertip-sized patch has 400 tiny needles that deliver the spike protein pieces into the skin. It goes on like a Band-Aid. The needles are built from sugars and the antigens, and they just dissolve.

“We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient,” said Louis Falo, co-senior author and professor and chair of dermatology at Pitt’s School of Medicine and UPMC. “And it’s actually pretty painless—it feels kind of like Velcro.”

They are currently submitting an Investigational New Drug (IND) with the U.S. Food and Drug Administration (FDA) and hope to begin Phase I human clinical trials in the next few months.

Genetic Mechanisms of Inflammatory Bowel Disease

Researchers at Children's Hospital of Philadelphia identified a genetic variant that causes the development of inflammatory bowel disease (IBD). The pathway is linked to other immune disorders. More than 240 genetic regions are already associated with IBD, but each region has multiple markers and not all are causative. The researchers focused on the single nucleotide polymorphism (SNP) rs1887428, located on the promoter region of the JAK2 gene. The protein coded by the gene controls the production of blood cells. The team found that two transcription factors, RBPJ and CUX1, recognize the DNA sequence altered by the rs1887428 SNP, and while it only has mild influence on JAK2 expression, it was amplified by other proteins in the JAK2 pathway.

Possible Mechanism of Link Between Obesity and Breast Cancer

Breast cancer (and other cancers) and obesity are associated, but the reason for that link isn’t well understood. Researchers from the University of Louisville published research suggesting that the fatty acid binding protein family, especially FABP4, plays a critical role. Fat tissue produces FABP4 within fat cells, which processes and distributes water-insoluble long-chain fatty acids. Normally, some FABP4 enters the bloodstream, but the higher fat volume, the more FABP4 is secreted. They believe two mechanisms are in play. Within cells, FABP4 increases in certain tumor-associated macrophages, which accumulate in tumors and promote cancer growth. And second, when elevated levels of FABP4 circulate outside the fat cells, it promotes breast cancer by directly interacting with breast cancer cells.

Using Cellular Machinery Without the Cells to Develop Drugs

Northwestern University and ShanghaiTech University leveraged cell-free synthetic biology to produce a drug that kills SARS-CoV-2 in cell cultures. They indicate they could create the new drug by taking the molecular machinery out of cells and using that machinery to make a product in a safe, cheap and quick way. The molecule is called valinomycin. By using this method, they were able to increase production yields more than 5,000 times in only a few quick design cycles.

Glucose Metabolism Linked to Alzheimer’s Disease

Researchers with the National Institutes of Health’s National Institute on Aging conducted the largest study so far on proteins related to Alzheimer’s and identified proteins and biological processes that regulate glucose metabolism that are associated with Alzheimer’s. The study was published in the journal Nature Medicine.

The study was part of the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD). The investigators assayed the levels and analyzed the expression patterns of more than 3,000 proteins in brain and cerebrospinal fluid samples collected at centers across the U.S.

“This is an example of how the collaborative, open science platform of AMP-AD is creating a pipeline of discovery for new approaches to diagnosis, treatment and prevention of Alzheimer’s disease,” said Richard J. Hodes, NIA director. “This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources.”

The study involved analyzing protein expression patterns in more than 2,000 human brain and almost 400 cerebrospinal fluid samples taken from both healthy individuals and Alzheimer’s patients. They analyzed how the protein modules relate to Alzheimer’s and other neurodegenerative diseases. They observed changes in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain tissues from both Alzheimer’s patients and people with documented brain pathology who were cognitively normal. This also would seem to support increasing evidence that brain inflammation is involved in the disease as well.

In Alzheimer’s patients, they found that how cells extract energy from glucose is increased in both the brains and spinal fluid of Alzheimer’s patients. The proteins observed were also elevated in preclinical Alzheimer’s patients, which is to say, people with brain pathology of the disease who had not shown cognitive decline.

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