By Julie Steenhuysen
CHICAGO May 23 Kathrin Jansen is a
microbiologist with at least two breakthrough vaccines to her
name: she brought the cervical cancer vaccine Gardasil to market
for Merck and helped develop the $4 billion a year pneumonia and
meningitis vaccine Prevnar 13 for Pfizer.
Jansen's next vaccine success could come by taming the
superbug MRSA, a drug-resistant bacterium that she has seen
ravage a healthy man up close and personally.
Methicillin-resistant Staphylococcus aureus infects an
estimated 53 million people globally and costs more than $20
billion a year to treat. In the United States alone, MRSA kills
20,000 Americans each year, exceeding annual deaths from AIDS.
Jansen watched the infection unfold two years ago when
visiting her stepfather, who was in the hospital for a hip
replacement. The man in the bed next door died soon after MRSA
attacked the vascular graft in his leg.
"He went in healthy and died very quickly," recalls Jansen,
senior vice president of vaccine research and early development
at Pfizer Inc, the world's largest drug maker. She says
the experience steeled her resolve to develop an effective
vaccine that could prevent such deaths.
But Staphylococcus aureus has proven a tenacious adversary.
In the past decade, vaccine candidates by Nabi
Biopharmaceuticals and Merck & Co Inc failed in costly,
late-stage clinical trials. Now, led by Jansen, Pfizer is taking
a shot. Competitors, including vaccine giants GlaxoSmithKline
, Novartis and Sanofi, are, too.
And while the race could lead to a viable vaccine,
potentially worth billions in sales, critics say companies may
be risking costly failure with so much work on a bacterium that
is still barely understood.
'BAG OF TROUBLE'
Staph has been living in and on its human hosts for
centuries. At any given time, 25 to 35 percent of individuals
will test positive for staph, often with no symptoms. But the
bacterium can cause a range of diseases from boils and impetigo
to raging blood infections and deadly bacterial pneumonia.
The discovery of penicillin in 1928 gave doctors a way to
defeat staph infections, but overuse and misuse gave rise to
drug-resistant staph. Methicillin was developed to overcome
drug-resistance, but by the 1960s, staph evolved new defenses to
overcome this more powerful version of penicillin.
Thus began the decades-long battle against
methicillin-resistant staph, now the most common cause of
hospital-acquired infections that is increasingly spreading into
army barracks, prisons and daycare centers.
Dr. Bill Gruber, a Pfizer senior vice president who led
clinical trials for Prevnar 13 and is running the company's
Staph aureus trials, thinks of the bacterium as "a little bag of
"Basically, it has a number of different toxins and defenses
to try to defeat you."
That may explain why vaccines from Nabi and Merck failed.
Both tried to defeat this bug by attacking on just one front.
The vaccine by Nabi, now Biota Pharmaceuticals,
focused only on the sugar capsule the bacteria make to hide from
the immune system, while Merck's focused on a single protein
that helps staph gets its nutrition. Neither lived up to
"We've learned that just focusing on one target of Staph
aureus might not be sufficient," said Dr. Buddy Creech, an
infectious diseases expert at Vanderbilt University.
IT TAKES STAMINA
Jansen has been working on a Staph aureus vaccine for the
past decade, first at Merck, then at Wyeth, and now at Pfizer.
The East German-born scientist - who fled to the West in
1960 and earned her PhD in biology at Philipps University in
Marburg - says it takes stamina to develop a successful vaccine,
a process that can take 15 years or more. With the cervical
cancer vaccine Gardasil, which had 2012 sales of $1.6 billion,
it took 14 years from lab bench to government approval. "That's
actually a fast development program," she said.
With Staph aureus, it took eight years from the first
experiments to human safety trials. Now, it could take another
seven to 10 years to wind up clinical trials, putting the team
about midway through the process.
Pfizer's initial vaccine targeted three mechanisms key to
staph's survival and ability to cause disease. Two of those
focused on sugar capsules. The third attacks a mechanism called
"clumping factor," which allows bacteria to stick to proteins
when they enter the body.
But Jansen's team wanted one more point of attack. They
added a fourth antigen, a protein that allows the bacterium to
steal manganese - a key nutrient - from host cells.
The result is a four-antigen vaccine that generates antibody
responses at distinct points of the life cycle of the bug. The
company is testing this in Phase 1/Phase 2 trials in healthy
adults in the United States.
If Pfizer gets the results they hope for, likely later this
year, the company expects to meet with regulators to iron out a
plan for larger trials involving thousands of individuals.
Initially, the vaccine would be aimed at preventing
infections in millions of people globally who need elective
procedures such as a hip replacement. Ultimately, it could be
used to protect people at risk in the broader community.
Pfizer is furthest along, but the large, untapped market,
estimated to be worth $3 billion to $4 billion a year, has drawn
interest from several companies.
GlaxoSmithKline has been quiet about its approach. The
drugmaker had been partnering with Nabi's failed StaphVax
candidate, and in 2009 bought another Nabi candidate called
PentaStaph for $46 million.
Company researchers declined to discuss their program, but
Glaxo spokeswoman Melinda Stubbee confirmed the company has a
four-component vaccine in Phase 1 development. "We are still
evaluating the data and haven't yet announced plans to present
the data or to pursue further development," she said.
NovaDigm Therapeutics, a private company based in Grand
Forks, North Dakota, is developing a single-antigen vaccine that
targets both staph and yeast infections caused by the fungus
Other rivals with early-stage programs include Novartis,
which has a vaccine in Phase 1 trials, and Sanofi, which is
partnering with privately held biotech Syntiron.
Although academic researchers applaud these efforts, they
say companies may be rushing into trials too soon, especially
when so much is unknown about how staph interacts with people.
"Our development of Staphylococcal vaccines has predated an
adequate understanding of the human response to infection,"
For instance, it is still not clear whether a Staph aureus
vaccine that protects against skin infections will also protect
individuals from bloodstream infections. It may be that instead
of preventing infection, some vaccines will merely blunt
Dr. Robert Daum, who leads the MRSA Research Center at the
University of Chicago Medical Center, doubts any of the current
candidates will make it into widespread use. "I am convinced we
need a vaccine. I'm just not sure anyone knows how to make one
Jansen, who knows Daum, said she understands his skepticism.
"I'm a microbiologist. I know bacteria pretty well. They are
very potent adversaries."
She says there's a reason the company was not the first out
of the gate. "We wanted to make sure that we looked under all
the rocks and found what we needed to find."
Tests in animals and people suggest the vaccine induces
production of antibodies that defeat staph's defenses and kill
the bacteria. "To our knowledge, we are the only ones who have
demonstrated very, very robust killing responses."
That was enough for Jansen. "We essentially said, 'That's
it. We put it together as best as we know how. Now is the time
to test it.'"