Findings Offer Alternative Approach to Creating a Universal Influenza Vaccine

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Since Prior Flu Exposure Dictates Your Future Immune Response, New Vaccine Regiments Can Be Rationally Developed, Researchers Say

A team of scientists, led by researchers at The Wistar Institute, has determined that it might be possible to stimulate the immune system against multiple strains of influenza virus by sequentially vaccinating individuals with distinct influenza strains isolated over the last century.

Their results also suggest that world health experts might need to re-evaluate standard tests used for surveillance of novel influenza strains.  Their findings are published in the Journal of Experimental Medicine.

According to the Wistar researchers, their analysis could lead to an alternative approach to creating a  “universal” flu vaccine—a vaccine that would provide resistance to seasonal and pandemic influenza strains over many years, negating the need for an annual flu shot.

“Influenza vaccines are very safe and provide good protection.  However, we need to continuously update seasonal flu vaccines because influenza viral proteins change over time,” said Scott Hensley, Ph.D., an assistant professor at The Wistar Institute and corresponding author on the study. “Since influenza viruses are constantly changing, we all have unique pre-exposure histories that depend on when we were born and the specific types of viruses that circulated during our childhood.”

Vaccines work by stimulating the immune system to produce antibody proteins against particles (called antigens) from an infectious agent, such as bacteria or a virus. The immune system saves the cells that produce effective antibodies, which then provide immunity against future attacks by the same or similar infectious agents.  Despite the availability of a vaccine, seasonal influenza typically kills 36,000 Americans, alone, and nearly a half million individuals around the world, in total.

Most current efforts to create universal vaccines hinge on the idea of generating antibodies against a portion of the virus that is relatively unchanged year-to-year.

“Our studies demonstrate that individuals that are infected sequentially with dramatically different influenza strains mount antibody responses against a conserved region of influenza virus,” Hensley said. “Since we now know that pre-exposure events can influence vaccine responsiveness in a predictable way, we can begin to design vaccine regiments that preferentially elicit antibody responses against conserved regions of influenza virus.”

The researchers began their current work by studying human antibody responses against the 2009 pandemic H1N1 virus. The 2009 strain is antigenically distinct from recently circulating seasonal H1N1 strains, and a distant relative of the virus that caused the devastating “Spanish Flu” of the early 20th century. The most effective antibodies are those that bind to a particular portion (or “epitope”) of hemagglutinin (HA), a protein produced by the influenza virus.

According to Hensley, however, their chief insight occurred when his team hit the “sort” button on a spreadsheet document, thereby arranging all samples by age of the donor. Different aged people, they found, mount vastly different antibody responses to pandemic H1N1, depending on whether or not they were exposed to a seasonal H1N1 years earlier. “We can now accurately predict how individuals will respond to the pandemic H1N1 strain based on the year that they were born,” Hensley said.

Their investigation also suggests that ferrets with no prior influenza exposure might not be the most reliable predictor of human immune responses.  Anti-sera—or blood containing antibodies–created in these “naïve” ferrets are commonly used for influenza surveillance.  The researchers found that naïve ferrets mount a response to an epitope in a decidedly different portion of HA than do most humans, but subsequently infecting these ferrets with other historical influenza strains can shift the antibody response toward the epitope that human antibodies recognize. This shift might also be replicable in humans through multiple infections or vaccinations, the researchers believe.

According to Hensley, one strategy would be to sequentially vaccinate children with antigenically distinct viral strains.  “Babies are born with an immunological blank slate,” Hensley said.  “We may be able to strategically vaccinate our children with antigenically diverse influenza strains to elicit antibodies against conserved viral epitopes.”

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via The Wistar Institute
 

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Influenza study: Meet flu virus’ new enemy

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Simon Fraser University virologist Masahiro Niikura and his doctoral student Nicole Bance are among an international group of scientists that has discovered a new class of molecular compounds capable of killing the influenza virus.

Working on the premise that too much of a good thing can be a killer, the scientists have advanced previous researchers’ methods of manipulating an enzyme that is key to how influenza replicates and spreads.

Their new compounds will lead to a new generation of anti-influenza drugs that the virus’ strains can’t adapt to, and resist, as easily as they do Tamiful. It’s an anti-influenza drug that is becoming less effective against the constantly mutating flu virus.

These increasingly less adequate anti-influenza drugs are currently doctors’ best weapons against influenza. They helped the world beat H1N1, swine flu, into submission four years ago.

The journal Science Express has just published online the scientists’ study, revealing how to use their newly discovered compounds to interrupt the enzyme neuraminidase’s facilitation of influenza’s spread.

Tamiful and another anti-influenza drug, Relenza, focus on interrupting neuraminidase’s ability to help influenza detach from an infected cell’s surface by digesting sialic acid, a sugar on the surface of the cell. The flu virus uses the same sugar to stick to the cell while invading it. Once attached, influenza can invade the cell and replicate.

This is where the newly discovered compounds come to the still-healthy cells’ rescue. They clog up neuraminidase, stopping the enzyme from dissolving the sialic acid, which prevents the virus from escaping the infected cell and spreading.

The new compounds are also more effective because they’re water-soluble. “They reach the patient’s throat where the flu virus is replicating after being taken orally,” says Niikura, a Faculty of Health Sciences associate professor.

“Influenza develops resistance to Replenza less frequently, but it’s not the drug of choice like Tamiful because it’s not water-soluble and has to be taken as a nasal spray.

“Our new compounds are structurally more similar to sialic acid than Tamiful. We expect this closer match will make it much more difficult for influenza to adapt to new drugs.”

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via Simon Fraser University
 

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Critically Ill Flu Patients Saved With Artificial Lung Technology Treatment Normally Used For Lung Transplant Patients

English: Bronchial anatomy detail of alveoli a...

The ECLS systems are essentially artificial lungs that oxygenate the patient’s blood outside the body

In recent weeks the intensive critical care units at University Health Network’s Toronto General Hospital have used Extra Corporeal Lung Support (ECLS) to support five influenza (flu) patients in their recovery from severe respiratory problems.  ECLS systems are normally used at the hospital as a bridge to lung transplantation but increasingly, the hospital is using ECLS on patients where the usual breathing machines (ventilators) cannot support the patient whose lungs need time to rest and heal.

The ECLS systems are essentially artificial lungs that oxygenate the patient’s blood outside the body, which gives lungs the chance to rest and heal.  This method of oxygenation means that a ventilator is not used to help the patient breath and also means that the patient is not exposed to the possibility of further lung injury, which can happen to ventilated patients.  The use of ECLS system requires expertise in its use to avoid other problems such as clots, bleeding problems and infections related to use of the device.

The lung is the only organ that, even when injured, is required to support the life of the patient while it is enduring the injury and trying to recover. The ventilators routinely used in this setting can actually add further injury to the lung on top of the original injury caused by the flu or pneumonia. This is where ECLS can play an important role by taking over the job of the lung so that the lung has a chance to be treated, rest and recover.

“ECLS is an important part of our ability to bridge patients to lung transplantation and we have a great deal of experience in its use,” said Dr. Shaf Keshavjee, who directs the ECLS Program as part of the Toronto Lung Transplant Program. Dr. Keshavjee is a thoracic surgeon and the Surgeon in Chief at University Health Network.  “As the technology has improved over the years, we are now able to offer this life-saving therapy to the small percentage of patients with influenza that get into severe trouble with acute lung injury.

This is part of our strategy to be prepared should we have a serious flu epidemic. The past few weeks have illustrated that our planning and training of our team has paid off. When several Ontario hospitals called us for help with their patients in serious lung failure, we were able to transfer those patients in and provide this life-saving therapy. All five patients survived to be weaned off the ECLS machines.”

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via University Health Network
 

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Method To Make One-Way Flu Vaccine Discovered

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With this breakthrough the immune system can learn to recognize any type of flu virus and attack the pathogen, preventing illness.

A new process to make a one-time, universal influenza vaccine has been discovered by a researcher at Georgia State University’s Center for Inflammation, Immunity and Infection and his partners.

Associate Professor Sang-Moo Kang and his collaborators have found a way to make the one-time vaccine by using recombinant genetic engineering technology that does not use a seasonal virus.

Instead, the new vaccine uses a virus’ small fragment that does not vary among the different strains of flu viruses.

By using the fragment and generating particles mimicking a virus in structure, the immune system can learn to recognize any type of flu virus and attack the pathogen, preventing illness. The research appears in a recent edition of the journal Molecular Therapy, published by the Nature Publishing Group.

“We can now design a vaccine that makes it easier to induce a good immune system response to recognize a pathogen, regardless of how the surface proteins of the virus change,” Kang said.

Health officials and scientists must alter flu vaccines every year to match expected strains, and often shortages can result, such as what happened during the 2009 Swine Flu outbreak. A one-time vaccine would prevent such a scenario, Kang said.

“Outbreaks of pandemic can be a dangerous situation, and our current vaccination procedures are not perfect,” he said.

Using the new one-time vaccine, using only a fragment rather than the live viral vaccine, such as FluMist, or a killed virus itself, would be safer for people with weakened immune systems, young children and the elderly, Kang said.

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via Georgia State University
 

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An advance toward a flu-fighting nasal spray

It may be a particularly useful agent against pandemics and emerging viral strains

In an advance toward development of a nasal spray that protects against infection with influenza and spread of the disease, scientists are reporting identification of a substance that activates the first-line defense system against infection inside the nose. They describe effects of a synthetic form of a natural substance found in bacterial cell walls in ACS’ journal Molecular Pharmaceutics.

David C. Jackson and colleagues explain that the body’s so-called innate immune system forms a first-line defense system against respiratory diseases like influenza A — which causes up to 1 billion infections and 500,000 deaths during seasonal epidemics. Those defenses swing into action almost immediately when viruses enter the nose and begin launching an infection. Scientists have been looking for ways to jump-start those defenses during flu outbreaks, and Jackson’s team turned to Pam2Cys. That synthetic lipoprotein, a substance consisting of a fat and a protein, has shown promise in activating the innate immune system.

The team found in laboratory tests that using Pam2Cys as a nasal spray primes the body’s immune system to fight infections. Importantly, they showed that the compound encourages but does not replace a normal immune response, which has been a concern about some anti-viral medicines. Because Pam2Cys stimulates the immune system against a wide spectrum of viral and bacterial attacks, the authors suggest it may be a particularly useful agent against pandemics and emerging viral strains.

The authors acknowledge funding from the National Health and Medical Research Council of Australia.

via American Chemical Society
 

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