Scientists discover how dengue vaccine fails to protect against disease
UNC-Chapel Hill scientists identified the small subpopulation of antibodies in vaccinated children that correlate with protection against dengue fever. This research should help shape better vaccines
2021-06-25
(Press-News.org) CHAPEL HILL, NC - Developing a viable vaccine against dengue virus has proved difficult because the pathogen is actually four different virus types, or serotypes. Unless a vaccine protects against all four, a vaccine can wind up doing more harm than good.
To help vaccine developers overcome this hurdle, the UNC School of Medicine lab of Aravinda de Silva, PhD, professor in the UNC Department of Microbiology and Immunology, investigated samples from children enrolled in a dengue vaccine trial to identify the specific kinds of antibody responses that correlate with protection against dengue virus disease. In doing so, the researchers discovered that a small subpopulation of antibodies binding to unique sites on each serotype are linked to protection. The research, published in the Journal of Clinical Investigation, provides important information for vaccine developers to consider when creating a dengue vaccine, which has long eluded scientists.
The four dengue virus serotypes are mosquito-borne flaviviruses that infect hundreds of millions of individuals each year in Southeast Asia, western Pacific Islands, Africa, and Latin America. Nearly 100 million individuals report flu-like symptoms. Though rarely deadly, the virus can cause severe illness, especially when a person who was previously infected with one serotype (and recovers) is then infected by a second serotype. This happens because antibodies from the first infection help the virus replicate during the second infection through a process called antibody dependent enhancement. A dengue vaccine induced antibody response weighted towards a single dengue virus serotype can mimic this phenomenon.
Several vaccines have been in clinical development for years, and most show that they induce neutralizing antibodies against all four serotypes. Yet, research has also shown that the creation of neutralizing antibodies alone does not correlate to protection against clinical disease. The de Silva lab conducted experiments to compare the properties of antibodies against wild-type Dengue viruses and the properties of antibodies produced by a leading vaccine candidate - Dengvaxia - which the pharmaceutical company Sanofi Pasteur created using all four dengue virus serotypes in one formulation.
Experiments led by Sandra Henein, research associate in the UNC Department of Microbiology and Immunology, and Cameron Adams, a medical and graduate student in the UNC Medical Scientist Training Program (MD/PhD), showed that wild type infections induced neutralizing and protective antibodies that recognized a part of the virus - an epitope - unique to each serotype. The vaccine, though, mainly stimulated neutralizing antibodies that recognized epitopes common among all serotypes. In vaccine trials, these antibodies did not protect children from dengue. In the past, researchers have considered all dengue neutralizing antibodies to be protective in people. This appears to not be the case, according to this UNC-led research.
"Our results suggest that a safe and effective dengue virus vaccine needs to stimulate neutralizing antibodies targeting unique sites on each of the four dengue serotypes ," Adams said. "Not merely the neutralizing antibodies against cross-reactive epitopes common to all four dengue types."
INFORMATION:
Henein and Adams are co-first authors of the JCI paper, and de Silva is senior author. Other authors are Matthew Bonaparte, Janice Moser, Alina Munteanu, all from Sanofi Pasteur, and Ralph Baric, from UNC-Chapel Hill.
The National Institute of Allergy and Infectious Diseases funded this work through R01 grants AI107731 and AI125198.
ELSE PRESS RELEASES FROM THIS DATE:
2021-06-25
UPTON, NY--Scientists have organized proteins--nature's most versatile building blocks--in desired 2-D and 3-D ordered arrays while maintaining their structural stability and biological activity. They built these designer functional protein arrays by using DNA as a programmable construction material. The team--representing the U.S. Department of Energy's (DOE) Brookhaven National Laboratory, Columbia University, DOE's Lawrence Berkeley National Laboratory, and City University of New York (CUNY)--described their approach in the June 17 issue of Nature Communications.
"For decades, scientists have dreamed about rationally assembling proteins into specific organizations with preserved protein function," ...
2021-06-25
Scientists from within the Antibody and Vaccine Group at the University of Southampton have gained novel insights into how an important class of immune receptors called tumour necrosis factor receptors (TNFR) are activated.
The work, published in the journal Communications Biology, investigates a class of receptors present on immune cells called TNFR. These receptors, such as CD40, 4-1BB and OX40, are key in helping the immune system fight pathogens and cancer cells. Accordingly, antibody drugs which are designed to specifically target and activate these receptors (called ...
2021-06-25
People with dementia receiving home health care visits are less likely to be readmitted to the hospital when there is consistency in nursing staff, according to a new study by researchers at NYU Rory Meyers College of Nursing. The findings are published in the journal Medical Care, a journal of the American Public Health Association.
Home health care--in which health providers, primarily nurses, visit patients' homes to deliver care--has become a leading source of home- and community-based services caring for people living with dementia. These individuals often have multiple chronic conditions, take several medications, and need assistance with activities of daily living. In 2018, more than 5 million Medicare beneficiaries received ...
2021-06-25
COLUMBUS, Ohio - Although the United States is the only wealthy nation that doesn't guarantee paid leave to mothers or fathers after the arrival of a new child, Americans endorse providing paid time off for parents nearly as much as people from other countries.
About 82% of Americans support paid maternity leave, just slightly less than the 86% who support it in 26 wealthy nations, a new study shows.
Where Americans differ from the rest of the world is that they are less supportive of government funding for paid leaves, prefer shorter leave times and are less supportive of paid leave for fathers.
"We find marked differences in how Americans want paid leave administered compared ...
2021-06-25
Singularities such as those at the centre of black holes, where density becomes infinite, are often said to be places where physics 'breaks down'. However, this doesn't mean that 'anything' could happen, and physicists are interested in which laws could break down, and how.
Now, a research team from Imperial College London and the Cockcroft Institute and Lancaster University have proposed a way that singularities could violate the law of conservation of charge. Their theory is published in Annalen der Physik.
Co-author Professor Martin McCall, from the Department of Physics at Imperial, said: "'Physics breaks down at a singularity' is one of the most famous statements in pop-physics. But by ...
2021-06-25
To make computer chips, technologists around the world rely on atomic layer deposition (ALD), which can create films as fine as one atom thick. Businesses commonly use ALD to make semiconductor devices, but it also has applications in solar cells, lithium batteries and other energy-related fields.
Today, manufacturers increasingly rely on ALD to make new types of films, but figuring out how to tweak the process for each new material takes time.
Part of the problem is that researchers primarily use trial and error to identify optimal growth conditions. But a recently published study -- one of the first in this scientific field -- suggests that using artificial intelligence (AI) can be more efficient.
In the ACS Applied ...
2021-06-25
ALBUQUERQUE, N.M. -- Like two superheroes finally joining forces, Sandia National Laboratories' Z machine -- generator of the world's most powerful electrical pulses -- and Lawrence Livermore National Laboratory's National Ignition Facility -- the planet's most energetic laser source -- in a series of 10 experiments have detailed the responses of gold and platinum at pressures so extreme that their atomic structures momentarily distorted like images in a fun-house mirror.
Similar high-pressure changes induced in other settings have produced oddities like hydrogen appearing as a metallic fluid, helium in the form of rain and sodium a transparent metal. But until now there has been no way to accurately calibrate these pressures and responses, the first step to ...
2021-06-25
Tsukuba, Japan - Organic light-emitting diodes (OLEDs) are widely used in display technology and are also being investigated for lighting applications. A comprehensive understanding of these devices is therefore important if their properties are to be harnessed to their full potential. Researchers from the University of Tsukuba have directly observed the photoexcited electron dynamics in an organic film using time-resolved photoelectron emission microscopy. Their findings are published in Advanced Optical Materials .
OLED displays are popular because they are bright, lightweight, and do not consume a lot of power. Their output is generated when an exciton--a combination of an electron and an electron hole--releases its energy. However, this ...
2021-06-25
Tokyo, Japan - A cell is composed of numerous organelles, each with a unique role that helps contribute to its overall functionality. The lysosome is an organelle that contains digestive enzymes and functions as a molecular garbage disposal and recycling center. Since the role of lysosome is crucial to maintain the cellular homeostasis, the lysosomal dysfunction causes neurodegenerative and metabolic diseases, cancer, as well as lysosomal storage disorders.
In a new article published in Autophagy, researchers at Tokyo Medical and Dental University (TMDU) performed a novel type of structural analysis to demonstrate how a certain molecular interaction is crucial for one lysosomal membrane protein to perform effectively.
LAMP1 (lysosomal-associated ...
2021-06-25
LA JOLLA, CA--Chemists at Scripps Research have solved a long-standing problem in their field by developing a method for making a highly useful and previously very challenging type of modification to organic molecules. The breakthrough eases the process of modifying a variety of existing molecules for valuable applications such as improving the potency and duration of drugs.
The flexible new method, for "directed C--H hydroxylation with molecular oxygen," does what only natural enzymes have been able to do until now. It's described in a paper this week in Science.
"We ...
LAST 30 PRESS RELEASES:
[Press-News.org] Scientists discover how dengue vaccine fails to protect against disease
UNC-Chapel Hill scientists identified the small subpopulation of antibodies in vaccinated children that correlate with protection against dengue fever. This research should help shape better vaccines
