"These studies show that a potentially protective neutralizing antibody against a viral disease is under the control of immunological tolerance," said Barton Haynes, M.D., director of the Center for HIV/AIDS Vaccine Immunology (CHAVI) at Duke University Medical Center and senior author of the study appearing in the online early edition of the Proceedings of the National Academy of Sciences. "This represents a new insight into the way HIV effectively evades detection by the B cell arm of the immune system and may offer new directions for vaccine design."
Over the years, scientists have assumed that B cells – one of the first lines of defense against infection – are simply not able to "see" the HIV virus. HIV has the ability to hide its most vulnerable parts from immune system surveillance, and researchers generally assumed that helped explain why B cells often took weeks and even months to arise following infection.
But several years ago, Duke researchers hypothesized that the antibodies required to broadly neutralize HIV may not be produced in the first place because the immune system "sees" them as a potential threat – due to their similarity to antibodies that promote autoimmune disease – and destroys them.
To see if this is indeed what happens, Laurent Verkoczy, Ph.D., assistant professor of medicine at Duke and the lead author of the study, and Haynes genetically engineered a mouse that could only produce B cells containing a rare but potent broadly neutralizing human antibody that is able to block HIV infection.
Researchers found that the mouse's immune system produced plenty of early stage B cells bearing this human neutralizing antibody on their surface but eliminated most of them before they had a chance to fully evolve into more mature B cells capable of secreting the antibody.
"This work may mean that we need to think and act very differently in envisioning how a successful vaccine may work," said Verkoczy. "The good news is that while about 85 percent of the "right" kind of B cells are eliminated, about 15 percent survive and wind up in circulating blood, but are turned off. One goal in vaccine design may be to figure out how to wake them up so they can go to work."
"We have now unveiled a major reason why members of this class of neutralizing antibodies are not routinely made: Our own immune systems block their production because they are perceived as potentially harmful, when in reality, they are not," said Haynes. "This is a very unusual way the virus has developed to evade the immune system."
Haynes says researchers plan on using the new mouse model to test ways to teach the immune system to enable the production of powerful neutralizing antibodies capable of blocking HIV.
The research was supported by the Bill and Melinda Gates Foundation, the Duke Center for AIDS Research, and grants from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Duke colleagues who contributed to the research include T. Matt Holl, Hilary Bouton-Verville, S. Munir Alam, Hua-Xin Liao and Garnett Kelsoe. Additional co-authors include Marilyn Diaz, from the National Institute of Environmental Health Sciences and Ying-Bin Ouyang, of Xenogen Biosciences.
Michelle Gailiun | EurekAlert!
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences