Researchers at the School of Medicine have
successfully used an experimental DNA-based vaccine to
protect against ragweed allergies, commonly known as hay
fever, after just six injections. Patients receiving the
vaccine showed an average 60 percent reduction in allergy
symptoms compared to those receiving a placebo.
The experimental therapy holds the promise of one day
eliminating the need for traditional allergy medicines
targeting allergy symptoms, such as nasal steroids and
antihistamines, and providing a safer, faster replacement
for immunotherapy regimens, which are costly and take years
to work, the researchers say.
The Johns Hopkins study, conducted during two fall
ragweed ("hay fever") seasons in Baltimore, enrolled 25
volunteers, ages 23 to 60, with a demonstrated history of
ragweed allergy. Fourteen people received the vaccine,
administered as six weekly shots, while 11 others received
placebo injections.
During the test period, allergic symptoms were
monitored and recorded, right down to how many times
volunteers sneezed and how often their noses ran. Compared
to the placebo group, those who received the vaccine
exhibited a 60 percent reduction in all their allergy
symptoms, including sneezing, runny nose, watery eyes and
itching.
Relief from allergic symptoms was as pronounced in the
second year as in the first, even though no more vaccine
was administered. Lead investigator Peter Creticos, medical
director of the
Johns Hopkins Asthma and Allergy Center, explained that
such prolonged relief is an important part of his team's
findings because it appears that the vaccine's efficacy
doesn't wear off quickly. A new study, currently under way,
will further examine the drug's lasting effects in a larger
group of participants.
Creticos' current findings are published in the Oct. 5
issue of the New England Journal of Medicine.
"This therapeutic intervention heralds a major advance
in the treatment of allergic rhinitis," Creticos said.
"Long-lasting relief can be achieved with a concise,
six-week injection regimen, as opposed to the current
tedious, four-to-five-year course of treatment with
allergen immunotherapy."
Investigators at the University of California, San
Diego had previously observed that a particular sequence of
DNA, derived from bacteria, shuts down a T-helper cell
called Th2 that is involved in the body's inflammatory
response. Creticos and his team, recognizing that allergic
disease is driven by Th2 inflammation, then embarked on a
series of studies to evaluate the effectiveness of using
this approach to treat allergies. The central question that
they sought to answer was, What would happen if the DNA
strand was linked to the most allergenic portion of the
ragweed pollen protein, which is the No. 1 cause of
seasonal allergies in North America?
Dynavax Technologies Corp., of Berkeley, Calif.,
developed the vaccine and funded several of Creticos' early
safety studies; during that period, Creticos was a paid
consultant of Dynavax. The current study was sponsored by
the Immune Tolerance Network, which receives its funding
from the National Institute of Allergy and Infectious
Diseases and the National Institute of Diabetes and
Digestive and Kidney Diseases.
Creticos said that the vaccine works in two ways: by
suppressing acute allergic reactions (such as sneezing) and
by helping the body better regulate chronic inflammation
(such as itchy eyes and a runny nose).
It is thought that the vaccine lessens the immune
system's excessive reactions to inhaled allergens by
stimulating protective cells that turn off the Th2 helper
cells. The Th2 helper cells send out signals for the body
to create more IgE, the protein largely responsible for
making allergy sufferers miserable throughout the entire
ragweed season. Someone allergic to ragweed has inherited
the ability to make too much IgE antibody when exposed to
inhaled allergens.
Additionally, the vaccine may activate specialized
immune cells known as "dendritic cells" that serve as
peacekeepers, maintaining balance by keeping inflammation
in check over the long term and breaking an otherwise
self-sustaining allergic cycle that Creticos calls
"Th2-orchestrated allergic inflammation."
"We are turning off an inappropriate or abnormal
allergic response and returning the body to normalcy,"
Creticos said. "Our hope is that we can one day provide a
long-term cure for hay fever and other chronic inflammatory
diseases."