Understanding the initial immune response after dengue virus infection

May 01, 2020

SILVER SPRING, Md. - A study led by scientists at the Walter Reed Army Institute of Research sheds new light on the body's initial response to dengue virus (DENV) infection, describing the molecular diversity and specificity of the antibody response. These results, published in EBioMedicine, a journal published by The Lancet, identify a heretofore unappreciated role for DENV-reactive IgA antibodies.

DENV is a member of the clinically-relevant Flavivirus genus alongside Zika virus, yellow fever virus and others. With four distinct serotypes, DENV is thought to infect between 280 and 550 million people worldwide every year.

While the majority of individuals suffering from dengue fever recover without showing severe symptoms or requiring extensive medical intervention, approximately 500,000 individuals per year develop severe dengue which has a mortality rate of up to 20%. Dengue is of particular concern for deploying Service Members, and the development of effective countermeasures to prevent dengue infection is a priority for the Department of Defense.

Subclinical exposure is a significantly complicating factor for public health and vaccine development, as those individuals previously exposed to one DENV serotype are at greater risk for severe symptoms than those with no previous exposure. Therefore, determining the previous exposure history of a patient experiencing symptoms of DENV infection can provide insight to the patient's risk of developing severe disease.

In this study, researchers used single cell RNA sequencing technology to measure the products of B cell plasmablasts, the antibody-producing cells found in greatest numbers immediately after DENV exposure. They also used a range of analyses to describe the ability of these antibodies to neutralize DENV and characterize their structure.

They discovered that IgA represented a significant fraction of antibodies expressed by B cell plasmablasts circulating after DENV infection, most dramatically in individuals experiencing their first DENV infection. "The fact that we observed such a profound IgA signature in individuals experiencing their first DENV infection may improve our ability to rapidly determine a patient's DENV exposure history and risk of developing severe disease" says Dr. Adam Waickman, the lead author on the study.

Though these data were generated from a small group of children, this is the first study to measure and characterize the entire output of plasmablasts without limitations to specific types of antibodies. These insights set the stage for future work to fully characterize the body's immune response to DENV, understand risk factors to severe dengue and ultimately could be critical to the development of new diagnostic tools as well as a safe, efficacious dengue vaccine.
-end-
The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70- 25.

Headquartered in Silver Spring, Maryland, the Walter Reed Army Institute of Research provides unique research capabilities and innovative solutions to a range of force health and readiness challenges currently facing U.S. Service Members, along with threats anticipated during future operations.

Walter Reed Army Institute of Research

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.