Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

coronavirus

COVID-19 vaccine-generated antibodies last at least 6 months

How long does COVID-19 vaccine-generated immunity last? New laboratory results provide a partial answer to that question.

Antibodies generated by a currently available COVID-19 vaccine declined over time, but remained at high levels in 33 study participants 6 months after vaccination, according to data published Tuesday in the New England Journal of Medicine.

The results could begin to inform public health decisions about COVID-19 booster vaccinations and how frequently people should receive them. In older study participants, antiviral antibody activity tended to decay more rapidly than in those aged 18-55.

From Doria-Rose et al (2021). Note that neutralizing antibody activity was (on average) higher at day 209 than on day 29, when the second vaccine dose was administered. It takes two weeks for the immune system to kick into high gear after the second shot.

Emory Vaccine Center’s Mehul Suthar, co-lead author of the brief report, said that the “correlates of protection” are not yet known from COVID-19 vaccine studies – that is, what levels of antiviral antibodies are needed to fend off infection. Other forms of immunity, such as T cells, could be contributing to antiviral protection as well.

He cautioned that the decay in antibody activity over time – not surprising in itself – may combine with increased prevalence of emerging SARS-CoV-2 variants that may allow viruses to escape the immune system’s pressure.

“Still, these are encouraging results,” Suthar says. “We are seeing good antibody activity, measured three different ways, six months after vaccination. There are differences between age groups, which are consistent with what we know from other studies.”

The findings come from analysis of samples from the Moderna mRNA-1273 phase I clinical trial, which began last year. Reports of clinical outcomes from Pfizer/BioNTech also indicate that their vaccine remains effective after six months.

Read more

Posted on by Quinn Eastman in Immunology Leave a comment

High antiviral antibody levels may herald pediatric COVID-19 complication

Measuring blood antibody levels against SARS-CoV-2 may distinguish children with multisystem inflammatory syndrome (MIS-C), which appears to be a serious but rare complication of viral infection, say researchers at Emory University School of Medicine and Children’s Healthcare of Atlanta.  

Children with MIS-C had significantly higher levels of antiviral antibodies – more than 10 times higher — compared to children with milder symptoms of COVID-19, the research team found.  

The results, published in the journal Pediatrics, could help doctors establish the diagnosis of MIS-C and figure out which children are likely to need extra anti-inflammatory treatments. Children with MIS-C often develop cardiac problems and low blood pressure requiring intensive care.

More information about this research here.

Infographic showing CDC criteria for the diagnosis of MIS-C. From Nakra et al via Creative Commons.

Read more

Posted on by Quinn Eastman in Immunology 2 Comments

Study finds ‘important implications’ to understanding immunity against COVID-19

New research from Emory University indicates that nearly all people hospitalized with COVID-19 develop virus-neutralizing antibodies within six days of testing positive. The findings will be key in helping researchers understand protective immunity against SARS-CoV-2 and in informing vaccine development.

The test that Emory researchers developed also could help determine whether convalescent plasma from COVID-19 survivors can provide immunity to others, and which donors’ plasma should be used.

The antibody test developed by Emory and validated with samples from diagnosed patients has demonstrated that not all antibody tests are created equal – and that neutralizing antibodies, which provide immunity, have specific characteristics. Emory’s study focused on those neutralizing antibodies, which can stop the virus from infecting other cells.

The findings are now available on MedRxiv, the preprint server for health sciences, and are not yet peer-reviewed.

In the study, researchers looked at antibodies against the receptor-binding domain (RBD), part of the spike protein on the outside of the virus. The RBD is what grips on to human cells and allows the virus to enter them. The researchers focused on antibodies against the RBD because the sequence of the RBD in SARS-CoV-2 distinguishes it from other coronaviruses that cause the common cold.

The receptor-binding domain, or RBD, is what grips on to human cells and allows the virus to enter them.

The initial 44 patient blood samples used in this study were from patients being treated for COVID-19 at Emory University Hospital and Emory University Hospital Midtown.

“These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines,” says Mehul S. Suthar, PhD, co-lead author and assistant professor of pediatrics at Emory University School of Medicine and Emory Vaccine Center. This study serves as the initial step in a much larger serology effort.

Read more

Posted on by Wayne Drash in Immunology Leave a comment

Emory launches study on COVID-19 immune responses

Emory University researchers are taking part in a multi-site study across the United States to track the immune responses of people hospitalized with COVID-19 that will help inform how the disease progresses and potentially identify new ways to treat it.  The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The study – called Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) – launched Friday. Investigators expect to enroll up to 2,000 individuals who have been hospitalized with the new coronavirus in 10 research locations across the country.

Participants will be followed for up to 12 months after their hospitalization to assess how well they recover and whether they develop durable immunity to the virus.

Nadine Rouphael, associate professor at Emory’s School of Medicine, is leading the investigation as part of NIAID’s Human Immunology Project Consortium (HIPC) and says the study aims to determine how certain immunological measures correspond to or even predict the clinical severity of COVID-19.

“The IMPACC study is a unique opportunity to leverage clinical data and samples with cutting edge technology,” Rouphael says. “By analyzing the immune responses of diverse participants enrolled in the study, we aim to better understand why some cases of COVID-19 worsen while other patients recover.”

As participants recover, investigators will continue evaluating their immune responses to see how they fare: Do they experience lingering symptoms, or do they get long-term protection against the virus? This effort is one of many clinical projects working to better understand how this novel disease affects people differently and determine optimal ways to treat COVID-19.

Researchers will recruit participants within 36 hours of their admission to the hospital and collect blood and nasal swabs throughout their hospitalization, and during follow-up clinic visits after discharge. When possible, researchers will also examine lower airway secretions collected from patients requiring a ventilator for breathing support. Participants can be co-enrolled in other studies, such as those evaluating experimental treatments for COVID-19.

Biologic samples from all study participants will be sent to a number of Core Laboratories for detailed analysis of various aspects of the immune response to the virus that causes COVID-19.

For more information on the U.S. government response to the COVID-19 pandemic, visit www.coronavirus.gov.

Posted on by Wayne Drash in Immunology, Uncategorized Leave a comment

Can blood from coronavirus survivors save the lives of others?

Donated blood from COVID-19 survivors could be an effective treatment in helping others fight the illness – and should be tested more broadly to see if it can “change the course of this pandemic,” two Emory pathologists say.

The idea of using a component of survivors’ donated blood, or “convalescent plasma,” is that antibodies from patients who have recovered can be used in other people to help them defend against coronavirus.

Emory pathologists John Roback, MD, PhD and Jeannette Guarner, MD, wrote about the prospects of using the donated blood in a commentary published in JAMA. Their article accompanied a small study in China of five patients on ventilators whose condition improved after they were treated with convalescent plasma.

“Deploying passive antibody therapies against the rapidly increasing number of COIVD-19 cases provides an unprecedented opportunity to perform clinical studies of the efficacy of this treatment against a viral agent,” the two wrote. “If the results of rigorously conducted investigations, such as a large-scale randomized clinical trial, demonstrate efficacy, use of this therapy also could help change the course of this pandemic.”

The patients in Shenzhen were also treated with other antiviral and antiinflammatory agents, and the study was too small to come to definite conclusions. Still, the Emory authors say, the Shenzhen study provides an example of an approach that should be tested on a larger scale. Read more

Posted on by Wayne Drash in Immunology, Uncategorized Leave a comment