Fighting Flu with Fungus

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Fighting Flu with Fungus

Neugenesis hopes an orange mold will produce a bird flu vaccine.

April 10, 2006 Print Issue

http://www.redherring.com/article.aspx?a=16390

A powdery orange mold first known for its 1843 infestation of French

bakeries has a special place in genetics. Neurospora crassa was used

to demonstrate that enzyme-mediated steps in biological pathways are

under genetic control. In other words, it showed the relationship

between genes and proteins, and brought geneticists and biochemists

into the same labs.

Neugenesis is a company focused on this mold and CEO W. Dorsey

Stuart believes he can use it to solve one of the world's major

impending problems: bird flu.

Travelers landing and taking off at San Francisco airport fly a

couple of hundred yards over Burlingame, California-based

Neugenesis' small lab containing orange fluff-filled flasks.

The company was formed in Hawaii in 1992 in order to fulfill the

conditions of a state research grant issued when Mr. Stuart was

assistant professor of genetics and molecular biology at the

University of Hawaii. It has steadily improved its fungal strains

since, and is developing them to produce antibodies with an unusual

degree of variation in their structures. With Neurospora's genome

sequence published in 2003—and having collaborated with Danish

biotech company Novozymes to produce antibodies since 2002—Mr.

Stuart and his team are now investing their energy and Band of

Angels funding into making vaccines.

Theoretically, fungi would make fantastic vaccine factories. They

have simple and cheap habits. They absorb the nutrition they need

through a cell wall and, if properly tweaked, secrete proteins such

as human antibodies and vaccines back out. Mr. Stuart says they have

an added benefit: The carbohydrates stuck on these secreted human

proteins are more similar to human ones than the carbohydrates

created in chicken eggs, the current standard method of vaccine

production. But Neurospora's most relevant characteristic is that

its cells happily fuse with one another to accommodate multiple,

different nuclei.

Neugenesis intends to use the latter attribute as a way of

assembling the parts of a flu vaccine. By developing various

recombinant strains of Neurospora, each for a different strain (and

some for potential new versions of the virus that do not yet exist

in nature), Neugenesis plans to produce a bank of would-be vaccine

ingredients. The company can then create whatever combination of

viral antigens is needed by fusing the cells of different fungal

strains together so that they secrete vaccine ingredients custom-

made to the type of viral threat.

Chasing the Flu

The influenza virus changes so quickly that the most important

strains are often different from one flu season to the next. This

means the Centers for Disease Control in Atlanta has to best guess

the identity of the next viral wave many months in advance in order

for egg-based vaccine manufacturers to finish production in time.

Partly inspired by the well-publicized manufacturing woes of Chiron,

Mr. Stuart filed a patent for his fungal vaccine production method

in October 2004.

It is quicker, too. " Within a month you'll have your vaccine ready

for production—instead of nine months—no chickens, no eggs, " he

says. The reduced time lag would also allow for redesigning and

manufacturing a new flu vaccine in the middle of the season,

according to whichever strains take hold.

In the last quarter, Neugenesis has turned its fungi to producing an

antigen to hemagglutanin 5, the H5 part of the H5N1 flu virus—and

most important component of a vaccine against it. CSO

Cambareri has also altered the fungus so that it deposits the

antigen in its orange spores rather than secretes it into solution,

opening up the possibility that a vaccine could be eaten, by birds

and humans, instead of injected. This could be a solution for

vaccinating large numbers of people in developing countries where

refrigerators are few and far between, since several communities

would deliberately grow the fungus on a soy press-cake to make it a

more palatable foodstuff.

To be sure, Neugenesis' technology is still early stage, and oral

vaccines—particularly those that do not contain live versions of a

virus—tend not to survive the acidity and enzyme activity of the

stomach. There are tricks to deal with this problem, however, such

as encapsulating the vaccine in a tiny, fatty bubble called a

liposome. But Neugenesis is still at the stage of signing with a

collaborator to run animal trials, most likely in China.

Despite the challenges, it appears the VC community is eager to back

companies developing products to counter pandemics. Kleiner Perkins

Caufield & Byers recently announced a $200-million fund designed to

accelerate innovations for what it called " worldwide pandemic

preparedness. "