Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

somatic hypermutation

Antibody diversity mutations come from a vast genetic library

Vaccine scientists want to nudge the immune system into producing antibodies that will protect us from infection. In doing so, they are playing with fire – in a limited way. With every healthy antibody response, a process of internal evolution takes place among B cells, the immune cells that produce antibodies. It’s called “somatic hypermutation.”

In the lymph nodes, individual B cells undergo an accelerated rate of mutation. It’s as if those B cells’ DNA were being cooked with radiation or mutagenic chemicals – but only in a few genes. Then the lymph nodes select the B cells with high-affinity antibodies.

Gordon Dale, a just-defended graduate student from Joshy Jacob’s lab in Emory Vaccine Center, has a new paper in Journal of Immunology that sheds light on how somatic hypermutation takes place in both mice and humans.

In particular, Dale and Jacob found that the mutations that occur in human and mouse antibody genes are not random. They appear to borrow information from gene segments that are leftovers from the process of assembling antibody DNA in B cells.

In a mix and match process called VDJ recombination, B cells use one of many V, D, and J segments to form their antibody genes. What Dale and Jacob were looking at occurs after the VDJ step, when B cells get stimulated as part of an immune response.

They analyzed the patterns of mutations in human and mouse antibody genes, and found that mutations tend to come together, in a way that suggests that they are being copied from leftover V segments. They call this pattern “tem Read more

Posted on by Quinn Eastman in Immunology Leave a comment

How antiviral antibodies become part of immune memory

Weapons production first, research later. During wartime, governments follow these priorities, and so does the immune system.

When fighting a bacterial or viral infection, an otherwise healthy person will make lots of antibodies, blood-borne proteins that grab onto the invaders. The immune system also channels some of its resources into research: storing some antibody-making cells as insurance for a future encounter, and tinkering with the antibodies to improve them.

In humans, scientists know a lot about the cells involved in immediate antibody production, called plasmablasts, but less about the separate group of cells responsible for the “storage/research for the future” functions, called memory B cells. Understanding how to elicit memory B cells, along with plasmablasts, is critical for designing effective vaccines.

EbolaBcells

Activated B cells (blue) and plasmablasts (red) in patients hospitalized for Ebola virus infection, with a healthy donor for comparison. From Ellebedy et al Nature Immunology (2016).

Researchers at Emory Vaccine Center and Stanford’s Department of Pathology have been examining the precursors of memory B cells, called activated B cells, after influenza vaccination and infection and during Ebola virus infection. The Ebola-infected patients were the four who were treated at Emory University Hospital’s Serious Communicable Disease Unit in 2014.

The findings were published Monday, August 15 in Nature Immunology.

“Ebola virus infection represents a situation when the patients’ bodies were encountering something they’ve never seen before,” says lead author Ali Ellebedy, PhD, senior research scientist at Emory Vaccine Center. “In contrast, during both influenza vaccination and infection, the immune system generally is relying on recall.”

Unlike plasmablasts, activated B cells do not secrete antibodies spontaneously, but can do so if stimulated. Each B cell carries different rearrangements in its DNA, corresponding to the specificity and type of antibody it produces. The rearrangements allowed Ellebedy and his colleagues to track the activated B cells, like DNA bar codes, as an immune response progresses. Read more

Posted on by Quinn Eastman in Immunology Leave a comment