Tag Archives: Influenza

Potential treatment for severe influenza found in Omega-3 fatty acids

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shutterstock_129688976Omega-3 fatty acids, which have an important role in promoting healthy growth and development, have made headlines in recent years for, among other things, their possible cardiovascular benefits. Found in high levels in fish oil, these fatty acids are the most consumed non-vitamin or non-mineral supplement in the US. Now, researchers have discovered another potential use for these fat building blocks: using them as a treatment for flu.

In a study published today in Cell, a modified omega-3 fatty acid known as protectin D1 was found to markedly increase the chances of survival in mice with infected with various strains of influenza, including the H1N1 strain behind the 2009 ‘swine flu’ epidemic.

“The authors show for the first time that [protectin D1] actually disrupts replication of influenza,” says Charles Serhan, an anesthesiologist at Brigham and Women’s Hospital in Boston. “It provides a natural template for new therapeutic development.”

When given microgram doses of protectin D1 intravenously 12 hours before and immediately after infection with a strain of influenza A, three out of eight treated animals survived past a two-week end point; by comparison, all seven control counterparts died within eight days. Mice infected with the 2009 strain of H1N1 swine flu fared even better when treated in this manner—all six survived, compared with only two out of six in the group that received only a saline solution.

Protectin D1 given two days post-infection appeared nearly as effective in preventing death in mice as Peramivir, an intravenous anti-viral drug marketed by BioCryst Pharmaceuticals of Durham, North Carolina. Approved in Japan and Korea for treating severe flu, Peramivir did not move past phase III clinical trials in the US for efficacy, but was subject to an emergency FDA authorization in 2009 as a treatment for H1N1 swine flu.

Remarkably, while less than half of treated animals survived past two weeks on either therapeutic alone after infection with influenza A, none died after receiving protectin D1 and Peramivir in conjunction.

In a petri dish model using human lung cells, protectin D1 appeared to reduce the virulence of influenza by blocking the export of viral mRNA from a cell’s nucleus, according to the new study. This is reflected in a massive decrease in the infection rate of cells.

Derived from omega-3 fatty acids, protectin D1 is one of a family of similar fat molecules with apparent antiinflammatory and antibiotic properties. Naturally produced, these compounds are thought to play a protective effect in the lung, brain and other organs. This study is the first to demonstrate anti-viral qualities for these molecules, with protectin D1 showing the greatest efficacy.

“I see this as opening a whole new avenue of research,” says Serhan, who was the first to characterize protectin D1 in 2007. He notes that this could represent a new class of antivirals that work by both reducing excessive inflammation and by disarming replication of the virus. The risk for side effects could be low as well since “it’s a natural mechanism,” says Serhan.

Many questions remain as to protecin D1’s therapeutic potential in humans, as well as if these omega-3 fatty acid-derived molecules could treat other types of viral infections. Future clinical trials and research are needed to prove efficacy and safety, says Serhan. For now, he recommends not over-doing it with fish oil supplements, until scientists know more about the underlying mechanisms. “You don’t want to be deficient in [omega-3], but I wouldn’t go the other direction. There could be unwanted side effects.”

Image: Shutterstock

EDITORIAL: A long pause

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A version of this editorial appears in the February 2013 issue of Nature Medicine.

Last January, scientists voluntarily imposed a pause on research that could lead to the generation of highly pathogenic avian influenza viruses with increased transmissibility to mammals. Now, new restrictions currently under debate further risk stalling progress in avian flu research.

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In late 2011, a firestorm erupted around two papers under peer review on highly pathogenic avian influenza (HPAI) H5N1 viruses. Both identified mutations that would permit airborne transmission of the viruses to ferrets. Although the viruses were not highly pathogenic in the ferrets, the papers sparked concerns that the mutant H5N1 viruses might have pandemic potential.

The concerns are not unwarranted given the history of H5N1 infections. The case fatality rate due to H5N1 in humans exceeds 50%, yet only 610 infections have been recorded since 2003, in part because of its low capacity for human-to-human transmission. However, there is fear that avian influenza could acquire the mutations necessary to rapidly transmit among humans, similar to seasonal influenza. Therefore, a better understanding of the mutations necessary to facilitate transmission of H5N1 in mammals and their effects on the fitness of the virus is considered by many to be crucial in developing countermeasures in the event of an avian flu pandemic.

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A universal problem: One virologist’s 20-year effort to challenge an imperfect flu test

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{credit}Bindu Marathe{/credit}

Recent headlines have promised that a ‘universal flu vaccine’ may be within reach, pointing to antibodies that offer broad protection in animal studies. But the scientists behind this effort had to first overcome great skepticism from their peers—as well as an imperfect laboratory test. Hannah Hoag reports on one virologist’s 20-year effort to challenge the tenets of the field.

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Influenza is the Lady Gaga of viruses: it reinvents itself each year, often in unexpected ways. But the flu virus is far more dangerous than an infectious tune. Although the flu usually manifests as a mild illness, the virus kills as many as 500,000 people worldwide each year, and it continues to provide a challenge from a vaccination standpoint. Whereas most vaccines for illnesses such as measles or polio offer years or decades of protection, influenza vaccines tend to work for only one season. The relentless refashioning means new influenza vaccines must be routinely reformulated, all at a cost to consumers and global health systems of more than $4 billion each year.

A new type of vaccine could be on the way. In the past few years, a flurry of papers has provided firm evidence of antibodies capable of neutralizing multiple subtypes of the influenza virus. Immunologists say that isolating such antibodies is the first step toward the creation of a universal influenza vaccine that protects against seasonal flu year after year—and possibly prevents hundreds of millions of deaths when the next influenza pandemic sweeps across the globe. Several such universal flu vaccines are already in early human clinical testing. But convincing the biology community of the existence and potential of such antibodies was an uphill battle, and one complicated by a ‘gold standard’ test that masked the key findings.

Yoshinobu Okuno, who has chased the dream of a universal antibody against flu since 1989, knows these challenges well. Okuno, a virologist at Osaka University in Japan, is now viewed by many experts in the field as an important and early champion of the idea. Yet his discovery two decades ago of a broad-acting antibody called C179 didn’t make waves at the time. “People didn’t pay attention to it,” says Ian Wilson, a structural biologist at the Scripps Research Institute in La Jolla, California. “In those days, most people weren’t thinking about broadly neutralizing antibodies that you could develop for flu.”

The very test that prompted Okuno to look for these special antibodies—a tool known as the hemagglutination inhibition assay—tripped up the efforts of others in the field. In hindsight, the fault in the assay provides a cautionary tale of how the shortcomings of a test can mean that biomedical researchers miss what they are not looking for.

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