Though theoretical, the work points to the critical importance of what has been a poorly appreciated aspect of the interaction between a virus and those naturally produced defensive proteins called antibodies that fight infection.
By manipulating this multi-stage interactive process -- known as antibody interference -- to advantage, the scientists believe it may be possible to design more powerful vaccines than exist today.
The findings are described in the May 11 online edition of the Proceedings of the National Academy of Sciences.
"We have proposed that antibody interference plays a major role in determining the effectiveness of the antibody response to a viral infection," said Ned Wingreen, a professor of molecular biology and a member of the Lewis-Sigler Institute for Integrative Genomics. "And we believe that in order to get a more powerful vaccine, people are going to want one that minimizes this interference."
Other authors on the paper include Simon Levin, the George M. Moffett Professor of Biology, and Wilfred Ndifon, a former graduate student in Levin's lab and first author on the paper.
When a virus like influenza attacks a human, the body mounts a defense, producing antibodies custom-designed to attach themselves to the virus, blocking it from action and effectively neutralizing its harmful effects on the body.
Analyzing data about viral structure, antibody types and the reactions between them produced by virology laboratories across the country, Ndifon noticed a perplexing pattern. He found that antibodies were often better at protecting against a slightly different virus, a close cousin, than against the virus that spurred their creation. This is known as cross-reactivity.
A closer look, using techniques that combine computing and biophysics, suggested that a phenomenon known as antibody interference was at play. It arises when a virus prompts the creation of multiple types of antibodies. During a viral attack, what then transpires is that antibodies vie with each other to defend the body and sometimes crowd each other out as they attempt to attach themselves to the surface of the virus.
Strangely, antibodies that are actually less effective at protecting the body against a specific virus are often equally adept at attaching themselves to the virus, blocking the more effective antibodies from doing their job. The scientists suggest that if a way can be found to weaken the binding of the less effective antibodies, then this might constitute a new approach to vaccine design. Indeed, the perplexing pattern of enhanced cross-reactivities observed by Ndifon can be attributed to viruses that differ only at the sites on their surfaces where the less effective antibodies bind. Such variants would make ideal vaccine strains, guiding the immune system to produce two distinct types of antibodies: effective ones that are well matched to and good at binding to the infecting virus, and ineffective ones that are poorly matched to and bad at binding to the infecting virus, and consequently stay out of the way.
Today, vaccine designers, such as those working on new forms of flu vaccines, center their efforts upon developing a weakened strain of a virus that matches as closely as possible the anticipated infecting strain. Patients are then inoculated with this attenuated virus to provoke the creation of antibodies that will protect against future attacks.
The Princeton scientists suggest their findings show that a better way might involve intentionally developing a vaccine strain that differs from the anticipated infectious virus at the sites where less effective antibodies bind. In this way, the ineffective antibodies would stay out of the way in the face of a real influenza virus, allowing the effective antibodies to more fiercely fight the dangerous infecting strain when it comes along.
The team does not expect to develop a vaccine but is hoping to inspire others. Wingreen is a theoretical physicist, Levin is a theoretical ecologist and Ndifon was a graduate student learning theoretical biology. "Our best bet is to express our ideas as clearly as we can and hope someone will find them interesting and do the necessary experiments to verify or disprove them," Wingreen said.
The research was supported by a Burroughs Wellcome graduate fellowship and by the Defense Advanced Research Projects Agency.
Kitta MacPherson | EurekAlert!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy