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4-in-1 flu shot may mean lifelong protection against the flu

A vaccine combining centralized ancestral genes from four major influenza strains appears to provide broad protection against the dangerous ailment, according to new research by a team from the Nebraska Center for Virology.

Mice protected by the unconventional vaccine survived exposure to lethal doses of seven of nine widely divergent influenza viruses. Those that received higher doses of the vaccine didn’t even get sick.

In contrast, mice that received traditional flu shots or nasal sprays all sickened and died when exposed to the same viruses. The deadly pathogens were able to evade the immune responses triggered by the traditional vaccines.

While it is too soon to say the approach could be successfully used in humans, it appears to be a promising avenue toward a universal flu shot, according to lead researcher Eric Weaver, an assistant professor in the School of Biological Sciences at the University of Nebraska-Lincoln.

Weaver said the study is the first to report on whether a universal flu shot could be created by using a combination of multiple genes shared at the ancestral level by flu strains circulating today.

“The ultimate goal is to be able to vaccinate once and provide lifelong protection,” Weaver said.

The Centers for Disease Control and Prevention estimates that 40 million Americans contracted influenza during the 2015-16 flu season and 970,000 people were hospitalized for the ailment. The agency estimated that vaccinations prevented about 1.9 million illnesses and 67,000 hospitalizations.

“To put this in other terms, our current influenza vaccine programs and technologies reduce influenza infections and hospitalizations by 4.75 percent and 6.9 percent, respectively,” Weaver said. “There is no doubt that there is a need for more effective vaccine technologies.”

Yet because the influenza virus mutates rapidly and because people, animals and birds often carry the virus without displaying symptoms, it’s been difficult to develop a vaccine with long-term effectiveness. The conventional influenza vaccine platform uses weakened or dead versions of the influenza virus to stimulate immunity against hemagglutinin (HA), a spike-shaped protein that extends from the surface of the virus and attacks cells.

According to a 2013 Clinical Microbiology Reviews article, the challenges of the conventional approach include predicting which flu strain will circulate in coming years; manufacturing and delivering safe, timely and adequate supplies; and poor responsiveness among the elderly, who often are the most vulnerable to influenza infection.

Conventional vaccines have been shown to be less than 60 percent effective when they’re successfully matched to the currently circulating strain. They’re far less effective when mismatched.

“An ideal influenza vaccine would be inexpensive, provide long-lasting immunity, require few immunizations and would work against all variants of the virus,” Weaver said.

Some experts say it could take until 2020 or 2025 before a universal flu vaccine is available.

Pursuit of a universal influenza vaccine has been difficult. Scientists are trying various approaches to better match vaccines to multiple viral strains. Other strategies include developing vaccines aimed at the virus’s protein coat, other proteins that have been found to be identical in multiple flu strains, or the stalk of the hemagglutinin protein rather than its head.

These approaches have shown promising results. However, Weaver said his study is the first to report the use of multiple centralized HA genes, identified using protein sequence analysis programs, to provide the greatest level of cross-protective immunity possible.

In the article published Nov. 2 in Scientific Reports, Weaver and his colleagues Amy Lingel and Brianna L. Bullard detail an approach they say is “scalable and translatable to humans and may provide the foundation for complete and long-lasting anti-influenza immunity.”

The idea arose from past research led by Dr. Bette Korber at Los Alamos National Laboratories to discover the ancestral genes for the Human Immunodeficiency Virus and to pinpoint when that virus jumped from monkeys to man. Weaver was involved with that effort while a post-doctoral researcher at Duke University School of Medicine. He and his colleagues decided to try a similar concept with the influenza virus, synthesizing genes that are central to influenza’s phylogenetic tree.

Instead of using weakened or deadened flu virus, his experiments at the Nebraska Center for Virology have used replication-defective Adenoviruses – which cause the common cold – that have been altered to carry what he calls consensus genes for H1, H2, H3 and H5 influenza strains. The vaccine is no longer capable of causing cold symptoms, but is still able to safely deliver the influenza vaccine genes.

“Our idea is that these centralized antigens can set up a foundation of immunity against influenza,” he said. “Because they are centralized and represent all the strains equally, they could provide a basis for immunity against all evolved strains.”

Weaver’s research is funded by a National Institutes of Health grant.

4-in-1 flu shot may mean lifelong protection against the flu

A vaccine combining centralized ancestral genes from four major influenza strains appears to provide broad protection against the dangerous ailment, according to new research by a team from the Nebraska Center for Virology.

Mice protected by the unconventional vaccine survived exposure to lethal doses of seven of nine widely divergent influenza viruses. Those that received higher doses of the vaccine didn’t even get sick.

In contrast, mice that received traditional flu shots or nasal sprays all sickened and died when exposed to the same viruses. The deadly pathogens were able to evade the immune responses triggered by the traditional vaccines.

While it is too soon to say the approach could be successfully used in humans, it appears to be a promising avenue toward a universal flu shot, according to lead researcher Eric Weaver, an assistant professor in the School of Biological Sciences at the University of Nebraska-Lincoln.

Weaver said the study is the first to report on whether a universal flu shot could be created by using a combination of multiple genes shared at the ancestral level by flu strains circulating today.

“The ultimate goal is to be able to vaccinate once and provide lifelong protection,” Weaver said.

The Centers for Disease Control and Prevention estimates that 40 million Americans contracted influenza during the 2015-16 flu season and 970,000 people were hospitalized for the ailment. The agency estimated that vaccinations prevented about 1.9 million illnesses and 67,000 hospitalizations.

“To put this in other terms, our current influenza vaccine programs and technologies reduce influenza infections and hospitalizations by 4.75 percent and 6.9 percent, respectively,” Weaver said. “There is no doubt that there is a need for more effective vaccine technologies.”

Yet because the influenza virus mutates rapidly and because people, animals and birds often carry the virus without displaying symptoms, it’s been difficult to develop a vaccine with long-term effectiveness. The conventional influenza vaccine platform uses weakened or dead versions of the influenza virus to stimulate immunity against hemagglutinin (HA), a spike-shaped protein that extends from the surface of the virus and attacks cells.

According to a 2013 Clinical Microbiology Reviews article, the challenges of the conventional approach include predicting which flu strain will circulate in coming years; manufacturing and delivering safe, timely and adequate supplies; and poor responsiveness among the elderly, who often are the most vulnerable to influenza infection.

Conventional vaccines have been shown to be less than 60 percent effective when they’re successfully matched to the currently circulating strain. They’re far less effective when mismatched.

“An ideal influenza vaccine would be inexpensive, provide long-lasting immunity, require few immunizations and would work against all variants of the virus,” Weaver said.

Some experts say it could take until 2020 or 2025 before a universal flu vaccine is available.

Pursuit of a universal influenza vaccine has been difficult. Scientists are trying various approaches to better match vaccines to multiple viral strains. Other strategies include developing vaccines aimed at the virus’s protein coat, other proteins that have been found to be identical in multiple flu strains, or the stalk of the hemagglutinin protein rather than its head.

These approaches have shown promising results. However, Weaver said his study is the first to report the use of multiple centralized HA genes, identified using protein sequence analysis programs, to provide the greatest level of cross-protective immunity possible.

In the article published Nov. 2 in Scientific Reports, Weaver and his colleagues Amy Lingel and Brianna L. Bullard detail an approach they say is “scalable and translatable to humans and may provide the foundation for complete and long-lasting anti-influenza immunity.”

The idea arose from past research led by Dr. Bette Korber at Los Alamos National Laboratories to discover the ancestral genes for the Human Immunodeficiency Virus and to pinpoint when that virus jumped from monkeys to man. Weaver was involved with that effort while a post-doctoral researcher at Duke University School of Medicine. He and his colleagues decided to try a similar concept with the influenza virus, synthesizing genes that are central to influenza’s phylogenetic tree.

Instead of using weakened or deadened flu virus, his experiments at the Nebraska Center for Virology have used replication-defective Adenoviruses – which cause the common cold – that have been altered to carry what he calls consensus genes for H1, H2, H3 and H5 influenza strains. The vaccine is no longer capable of causing cold symptoms, but is still able to safely deliver the influenza vaccine genes.

“Our idea is that these centralized antigens can set up a foundation of immunity against influenza,” he said. “Because they are centralized and represent all the strains equally, they could provide a basis for immunity against all evolved strains.”

Weaver’s research is funded by a National Institutes of Health grant.

4-in-1 flu shot may mean lifelong protection against the flu

4-in-1 flu shot may mean lifelong protection against the flu

How a concussion’s effects endure, long after symptoms fade

It’s clear what happens during a concussion: First, there’s a violent collision that twists the brain inside of the skull. That sends the brain’s neurons into chaos, often leaving the victim confused, dizzy and with blurred vision.

More difficult to understand is how quickly the brain begins to return to normal after those initial symptoms fade.

It’s been generally assumed that the brain begins to repair itself quickly – within days or weeks of the injury. New research from the University of Nebraska-Lincoln, however, shows that undesirable effects can linger much longer among those with a history of concussions.

Scientists from the Center for Brain, Biology and Behavior at Nebraska used high-density electroencephalography, or EEG, to map and time electrical activity in the brain among two groups of male athletes – those with a history of concussions, and those without. They discovered that athletes who had suffered concussions at least a year earlier displayed cognitive responses one-tenth to two-tenths of a second slower than those who were concussion-free. In cognitive terms, that gap is “a really big deficit,” said Dennis Molfese, professor of psychology at Nebraska and an author of the study.

They also found the post-concussive athletes had to engage larger areas of their brains to complete memory tasks.

“For those with a concussion, at least a year post-injury, their brains haven’t figured it out yet,” Molfese said.

Because the athletes had, on average, suffered concussions years before the study, and because the results are similar to work Molfese and colleagues published in 2013 to test athletes immediately after a suspected concussion, the new study’s results suggest that while noticeable symptoms may subside, cognitive delays may never go away post-concussion.

The findings are another reason concussions should be taken seriously by coaches, trainers, parents and doctors, Molfese said.

“A concussion is brain damage,” he said. “The brain’s design is incredible; up to a certain point it is able to compensate. But if you keep piling on the injuries, it loses that ability.”

Molfese said the brain is constantly forming pathways of electrical activity between neurons to learn, grow and understand the world. As regular actions are performed, these circuits are shortened and are usually relegated to a few areas of the brain, which makes the brain an efficient, constantly improving machine.

That all changes with a concussion, which alters the brain’s cognitive pathways — which are in turn forced to reorganize away from damaged areas. Molfese said that “reorganization” is likely creating the cognitive delays and processing difficulties among study participants.

“Engaging more areas and forming new pathways take time,” he said. “When you pull in other brain areas, the brain has to learn how to make a new network it has already spent years developing.”

The Center for Brain, Biology and Behavior, or CB3, is an interdisciplinary center at Nebraska that brings together faculty in the social, biological and behavioral sciences and engineering. The center’s state-of-the-art facilities and multidisciplinary environment expands understanding of brain function and its effects on human behavior. The center’s unique capabilities and partnership with Nebraska Athletics deepen the university’s research capacity, including its leading expertise in concussion research.

The study, which was published by the International Journal of Psychophysiology, was co-authored by Caitlin Hudac of the University of Washington, Cathryn Cortesa of Johns Hopkins University and Patrick Ledwidge of Baldwin Wallace University. Hudac, Cortesa and Ledwidge all earned degrees from Nebraska.

How a concussion’s effects endure, long after symptoms fade

It’s clear what happens during a concussion: First, there’s a violent collision that twists the brain inside of the skull. That sends the brain’s neurons into chaos, often leaving the victim confused, dizzy and with blurred vision.

More difficult to understand is how quickly the brain begins to return to normal after those initial symptoms fade.

It’s been generally assumed that the brain begins to repair itself quickly – within days or weeks of the injury. New research from the University of Nebraska-Lincoln, however, shows that undesirable effects can linger much longer among those with a history of concussions.

Scientists from the Center for Brain, Biology and Behavior at Nebraska used high-density electroencephalography, or EEG, to map and time electrical activity in the brain among two groups of male athletes – those with a history of concussions, and those without. They discovered that athletes who had suffered concussions at least a year earlier displayed cognitive responses one-tenth to two-tenths of a second slower than those who were concussion-free. In cognitive terms, that gap is “a really big deficit,” said Dennis Molfese, professor of psychology at Nebraska and an author of the study.

They also found the post-concussive athletes had to engage larger areas of their brains to complete memory tasks.

“For those with a concussion, at least a year post-injury, their brains haven’t figured it out yet,” Molfese said.

Because the athletes had, on average, suffered concussions years before the study, and because the results are similar to work Molfese and colleagues published in 2013 to test athletes immediately after a suspected concussion, the new study’s results suggest that while noticeable symptoms may subside, cognitive delays may never go away post-concussion.

The findings are another reason concussions should be taken seriously by coaches, trainers, parents and doctors, Molfese said.

“A concussion is brain damage,” he said. “The brain’s design is incredible; up to a certain point it is able to compensate. But if you keep piling on the injuries, it loses that ability.”

Molfese said the brain is constantly forming pathways of electrical activity between neurons to learn, grow and understand the world. As regular actions are performed, these circuits are shortened and are usually relegated to a few areas of the brain, which makes the brain an efficient, constantly improving machine.

That all changes with a concussion, which alters the brain’s cognitive pathways — which are in turn forced to reorganize away from damaged areas. Molfese said that “reorganization” is likely creating the cognitive delays and processing difficulties among study participants.

“Engaging more areas and forming new pathways take time,” he said. “When you pull in other brain areas, the brain has to learn how to make a new network it has already spent years developing.”

The Center for Brain, Biology and Behavior, or CB3, is an interdisciplinary center at Nebraska that brings together faculty in the social, biological and behavioral sciences and engineering. The center’s state-of-the-art facilities and multidisciplinary environment expands understanding of brain function and its effects on human behavior. The center’s unique capabilities and partnership with Nebraska Athletics deepen the university’s research capacity, including its leading expertise in concussion research.

The study, which was published by the International Journal of Psychophysiology, was co-authored by Caitlin Hudac of the University of Washington, Cathryn Cortesa of Johns Hopkins University and Patrick Ledwidge of Baldwin Wallace University. Hudac, Cortesa and Ledwidge all earned degrees from Nebraska.