Inhalable measles vaccine will remove need for injections
7 May 2010
A new form of measles vaccine in an inhalable dry powder could
remove the need for syringes, making vaccination more acceptable to
patients and safer.
The inhalable vaccine was developed by a team of researchers led by
the University of Colorado at Boulder and will enter human clinical
trials later this year in India. It will lead to other inhalable,
inexpensive vaccines for illnesses ranging from tuberculosis to
cervical cancer.
The inhalable measles vaccine involves mixing "supercritical"
carbon dioxide with a weakened form of the measles virus. The
process produces microscopic bubbles and droplets that are dried to
make the inhalable powder, which is dispensed into the mouths of
patients using a small, cylindrical plastic sack with an opening
like the neck of a plastic water bottle.
Chemistry and Biochemistry Professor Robert Sievers of the
University of Colorado at Boulder said "Clinical trials are the next
vital step in making this vaccine widely available. One of our
primary goals of this project is to get rid of needles and syringes,
because they frighten some people, they hurt, they can transmit
diseases and there are issues with needle disposal.
"With the new technology, the inhaled powder is sent directly
into the lungs, a good target since measles attacks through the
respiratory tract. A person taking a deep breath from the sack is
effectively vaccinated."
Sievers will give a presentation on the subject at the Eighth
European Conference on Supercritical Fluid Applications to be held
May 9-12 in Graz, Austria.
According to the World Health Organization, measles is one of the
leading causes of death among young children. In 2008 there were an
estimated 164,000 measles deaths in children worldwide — nearly 450
deaths a day — and India accounts for about two-thirds of global
measles deaths in infants and children.
Phase One of the clinical trials to test the safety and efficacy
of the measles inhalant product are due to start this summer in Pune,
India, and will involve about 180 people. Phase Two of the India
clinical trials are expected to involve a larger number of patients.
Sievers, also a fellow at CU's Cooperative Institute for Research
in Environmental Sciences, said the measles vaccine development idea
grew out of atmospheric chemistry research he and his students were
conducting. The team was attempting to determine the chemistry of
specific air pollutants in particular regions of the world and how
people inhale and process tiny airborne droplets of pollutants.
As part of the measles project, Sievers and his students and
colleagues invented and patented a device known as the Carbon
Dioxide Assisted Nebulization with a Bubble Dryer, or CAN-BD, in
which two mixed streams of fluid are rapidly expanded to atmospheric
pressure where the tiny bubbles and droplets are dried by mixing
them with warm nitrogen. The resulting, inhalable-sized vaccine bits
are embedded in micro-particles of sugars and amino acids.
Aktiv-Dry is a Boulder spinoff company Sievers co-founded in 2002
with Professor John Carpenter of the University of Colorado School
of Pharmacy and Brian Quinn, current president of Aktiv-Dry. The
company, which employs about 10 people including former CU-Boulder
students, currently is developing CAN-BD for the marketplace.
"This project came out of the University of Colorado, and Aktiv-Dry
is partially owned by the university through the University of
Colorado Technology Transfer Office," said Sievers. "I've had 40
CU-Boulder students who have earned their doctorates under me
through the years, and it was those students and their work that
really positioned us at the right time to gain significant funding
for this project."
The US$20 million Aktiv-Dry research effort is funded by the
Grand Challenges in Global Health Initiative, which was created by
the Bill and Melinda Gates Foundation through the Foundation for The
National Institutes of Health. Sievers' project addresses one of the
14 Grand Challenges — the needle-free administration of vaccines by
pulmonary or nasal aerosols.
David H. McAdams, a CU-Boulder doctoral student in the chemistry
and biochemistry department working with Sievers, said he switched
his academic focus from atmospheric chemistry particle analytics to
participate in the measles project. "I saw an opportunity to use the
analysis of such particulates to benefit mankind and to help save
children by using inhalable vaccines."
The CU team recently tested the durability of the inhalant
vaccine by shipping a batch from the Serum Institute of India to
CU-Boulder, then shipping the same batch two months later to the
East Coast and back to Boulder. The vaccine proved to be stable
throughout the shipping process, indicating it likely would be
effective under challenging environmental conditions encountered in
developing nations, Sievers said.
The cost of an inhalant dose for measles is about 26 cents —
roughly the cost for an injectable form of the dose. The new
technology could potentially be used to deliver tiny antibiotics
particles to treat people with multi-resistant tuberculosis, said
Sievers. While the antibiotic inhalant would likely be combined with
oral doses and injections, the use of CAN-BD would direct the
antibiotic directly to the lungs where the disease is focused, said
Sievers.
Another potential use for the CAN-BD technology is treating human
papilloma virus, a sexually transmitted disease that causes cervical
cancer. "More women in India today die of cervical cancer than from
breast cancer, which is a much bigger killer in the United States,"
he said. Current treatment for papilloma virus is a three-dose
injection regimen that costs about US$300, a cost Sievers and his
group would like to lower significantly for it to be distributed to
women who need it in developing nations.
Collaborators on the measles project include scientists from the
Centers for Disease Control and Prevention in Atlanta, the National
Jewish Medical and Research Center in Denver, Johns Hopkins
University in Baltimore, the University of Kansas, the Serum
Institute of India in Pune, BD Technologies in Research Triangle
Park, N.C., and Seattle Genetics in Seattle.