Madison startup company mounting two-pronged attack against influenza

April 22, 2013

by David Tenenbaum

As a new type of "bird flu" causes deaths and worries in China, a Madison startup is attacking the problem on two fronts. FluGen, under the scientific guidance of UW-Madison researcher Yoshihiro Kawaoka, a world authority on influenza, is moving ahead with a better way to deliver existing vaccines and a novel "universal" flu vaccine.

Photo: Yoshihiro Kawaoka

Kawaoka

The vaccine — an outgrowth of Kawaoka's work at UW-Madison — could confer stronger immunity to a wide range of influenza viruses. In studies recently completed in conjunction with the National Institutes of Health, the company found strong protection in ferrets — commonly used to model influenza — against matching strains of influenza, including the deadly H5N1 "bird flu."

But FluGen's vaccine also protected animals from deadly challenge with a "mismatched" vaccine.

FluGen's vaccine contains a replicating live virus that is intended to alert the entire immune system. The vaccine "mimics the real deal, a real infection, because it enters the body just like a real flu virus does, through the nose," says company president and CEO Paul Radspinner. "But the key is that it doesn't multiply and make you sick.

"Current vaccines use dead virus that is injected into your arm," Radspinner says, "while ours is sprayed into the nose, so the body mounts a more realistic and natural immune response."

Influenza mutates millions of times faster than most viruses, creating new strains that outrun the immune system, Radspinner says. Some of these mutants, like the 1918 "Spanish flu," can cause horrific pandemics. Others, like the seasonal flu, are less destructive but still account for up to a half-million deaths around the world per year.

FluGen was formed in 2007 to commercialize discoveries by Kawaoka, and now has eight employees at new headquarters in the UW's University Research Park. The company is on the verge of initiating human clinical trials with a micro-needle injection device that delivers vaccine to the skin virtually pain-free. "Many of the immune responses in the skin are much stronger than in the muscle," says Radspinner. "The skin's primary role is defense against invading organisms."

It's unusual for a young company to engage in two separate lines of development, Radspinner admits, but the key is this: "We are seeking stronger immunity, both in terms of the way we deliver vaccine, and in the nature of the vaccine itself. This is important work because the current flu shot just isn't as effective as it should be."

“We are seeking stronger immunity, both in terms of the way we deliver vaccine, and in the nature of the vaccine itself. This is important work because the current flu shot just isn’t as effective as it should be.”

Paul Radspinner

The nasal spray of "single replication" vaccine is based on Kawaoka's discovery that removing part of a certain gene prevents the flu virus from reproducing multiple times inside human cells.

"The best way to prevent flu next year is to get infected with the flu this season," says Kawaoka. "If you get the flu today, the odds of getting another infection, even of a different type, are relatively low, because the body is very good at creating a broad immune response to the flu virus.

"This vaccine starts out like a regular flu infection," Kawaoka adds. "The virus enters the cell, where it would normally create hundreds of virus particles, but it stops right there. The immune system is alerted as if you are truly infected, but because the virus can't replicate, you get no flu symptoms. The idea is to create an immune response that is similar to a real flu infection, without making you sick."

The recent ferret tests show that vaccination with the single-replication H1N1 (seasonal influenza) strain produced cross-protection against deadly bird flu, Radspinner says. When the vaccine was delivered in two doses, every ferret survived infection with virtually no symptoms — whereas all of the unvaccinated ferrets died from the same challenge with H5N1 influenza.

A standard flu vaccine can only protect against those strains of virus it contains. "If I give you an H1N1 vaccine this year and a different H1N1 or an H3N2 strain comes along, you are likely to get sick," says Radspinner. "So far, based on what we have seen in mice and ferrets, this vaccine has much broader coverage."

Existing influenza vaccines contain a virus that was chopped up and killed, Radspinner says. "After it's injected, the body looks at it, says, 'I think it's the flu, but I'm not sure, I guess we should send some of our immunity guys after it.' After delivery of our new universal vaccine, the alarm bells go off: 'Holy cow, that looks like the flu!'"