Tag Archives: ACE2
Researchers from Cleveland Clinic’s Global Center for Pathogen Research & Human Health have developed a promising new COVID-19 vaccine candidate that utilizes nanotechnology and has shown strong efficacy in preclinical disease models.
According to new findings published in mBio, the vaccine produced potent neutralizing antibodies among preclinical models and also prevented infection and disease symptoms in the face of exposure to SARS-CoV-2 (the virus that causes COVID-19). An additional reason for the vaccine candidate’s early appeal is that it may be thermostable, which would make it easier to transport and store than currently authorized COVID-19 vaccines.
“Our vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin–a protein found in almost all living organisms,” said Jae Jung, PhD, director of the Global Center for Human Health & Pathogen Research and co-senior author on the study. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control.”
Added Dokyun (Leo) Kim, a graduate student in Dr. Jung’s lab and co-first author on the study, “This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries.”
Other benefits of the protein nanoparticles include minimizing cellular damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, like influenza.
The team’s vaccine uses the ferritin nanoparticles to deliver tiny, weakened fragments from the region of the SARS-CoV-2 spike protein that selectively binds to the human entry point for the virus (this fragment is called the receptor-binding domain, or RBD). When the SARS-CoV-2 RBD binds with the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to replicate.
The researchers tested their vaccine candidate on a ferret model of COVID-19, which reflects the human immune response and disease development better than other preclinical models. Dr. Jung, a foremost authority in virology and virus-induced cancers, previously developed the world’s first COVID-19 ferret model–a discovery that has significantly advanced research into SARS-CoV-2 infection and transmission.
From the outset of the pandemic, data coming out of early coronavirus hot spots like China, Italy, and New York City foretold that certain groups of people would be more vulnerable to Covid-19. The disease hit older people and people with underlying medical conditions the hardest. As early as February, diabetes had emerged as one of the conditions associated with the highest risk. In one large study out of China, people with diabetes were more than three times as likely to die of Covid-19 than the overall population.
But that’s not what brought four diabetes experts from Australia and the United Kingdom onto a Zoom call back in April. They were supposed to just be catching up—a virtual tea among friends. But talk soon turned to something strange that they’d been seeing in their own hospitals and hearing about through the grapevine. The weird thing was that people were showing up in Covid-19 wards, after having tested positive for the virus, with lots of sugar in their blood. These were people with no known history of diabetes. But you wouldn’t know it from their lab results.
After that call, the experts reached out to colleagues in other countries to see if they’d seen or heard of similar cases. They had. Acute viral infections of all sorts can stress the body, causing blood sugar levels to rise. So that in itself wasn’t unusual, says Francesco Rubino, a bariatric surgeon and diabetes researcher at King’s College in London, who was on that first Zoom call. “What we were seeing and hearing was a little bit different.”
Doctors around the world had described to him strange situations in which Covid-19 patients were showing symptoms of diabetes that didn’t fit the typical two-flavor manifestation of the disease. In most people with type 1 diabetes, their immune cells suddenly turn traitorous, destroying the cells in the pancreas that produce insulin—the hormone that allows glucose to exit the bloodstream and enter cells. People with type 2 diabetes have a different problem; their body slowly becomes resistant to the insulin it does produce. Rubino and his colleagues were seeing blended features of both types showing up spontaneously in people who’d recently been diagnosed with Covid-19.
“That was the first clinical puzzle,” he says. For clues to an explanation, Rubino and his colleagues looked to ACE2, the protein receptor that SARS-CoV-2 uses to invade human cells. It appears in the airways, yes, but also in other organs involved in controlling blood sugar, including the gut. Doctors in China discovered copies of the coronavirus in the poop of their Covid-19 patients. And a meta-analysis found that gastrointestinal symptoms plague one out of 10 Covid-19 sufferers.
In the last few decades, scientists have discovered that the gut is not the passive digestive organ once thought. It actually is a major endocrine player—responsible for producing hormone signals that talk to the pancreas, telling it to make more insulin, and to the brain, ordering it to make its owner stop eating. If the coronavirus is messing with these signals, that could provide a biological basis for why Covid-19 would be associated with different forms of diabetes, including hybrid and previously unknown manifestations of the disease. Rubino is one of a growing number of researchers who think that the relationship between the coronavirus and diabetes is actually a two-way street. Having diabetes doesn’t just tip the odds toward contracting a worse case of Covid-19. In some people, the virus might actually trigger the onset of diabetes, and the potential for a lifetime of having to manage it.