Aktiv-Dry Selected for a $19.5 Million
Grant from the Foundation for the
National Institutes of Health
Aktiv-Dry Needle-Free Delivery Grand Challenges
Project
The development of a needle-free delivery system for measles vaccine
supports the Grand Challenges in Global Health initiative and may serve as
a model to be adopted for other childhood vaccines.
Aktiv-Dry LLC, in collaboration with an extensive worldwide team, has been
selected for a $19.5 million grant from the Foundation for the National Institutes
of Health to support the development of an inhalable aerosol measles vaccine.
The project is among 43 groundbreaking research projects to improve health in
developing countries, supported by $436 million from the Grand Challenges in
Global Health initiative.
The Grand Challenges initiative was launched by the Bill & Melinda Gates
Foundation in 2003, in partnership with the National Institutes of Health, with a
$200 million grant to the FNIH and is a major international effort to achieve
scientific breakthroughs against diseases that kill millions of people each year in
the world’s poorest countries. It is funded with a $450 million commitment from
Gates Foundation, $27.1 from the Wellcome Trust, and $4.5 million from the
Canadian Institutes of Health Research (CIHR). The initiative is managed by
global health experts at the Foundation for NIH, the Gates Foundation, the
Wellcome Trust, and CIHR.
Aktiv-Dry and its worldwide team of collaborators are determined to
develop a safe, convenient, inhalable measles vaccine for use in
developing countries.
Measles—a vaccine-preventable disease—remains a major health burden
specifically in developing countries. The World Health Organization (WHO)
estimates that more than 2000 people die every day from measles, and most of
these deaths are poor children who live without electricity and refrigeration in
climates where injected liquid vaccines are not thermally stable. While syringe
and needle are most often used to administer vaccines, international authorities
recognize a growing requirement for alternative delivery systems that are simple
to administer, safe from spreading disease, and don’t require refrigeration.
The goal for the Aktiv-Dry team is to provide an effective inhalable measles
vaccine delivery at a cost that is equal to or less than percutaneous
administrations. The work on measles vaccine may serve as a model and be
adapted to other childhood vaccines.
The project led by Aktiv-Dry has three objectives. The first objective is to
synthesize a dry powder measles vaccine that can be administered to the
respiratory tract by inhalation. The second is to design and fabricate one or two
inexpensive, single-dose devices that effectively deliver these patented
microparticles to the pulmonary tract. The third objective is to assess safety in
Rhesus primates and to evaluate the vaccine and device with human subjects in
Phase I clinical trials in India.
Wet inhaled measles aerosol vaccine has been shown to be immunogenic, and
the Aktiv-Dry team will seek to determine whether the thermally stable dry
powder formulation elicits a similar clinical profile, while offering additional
advantages of stability.
In joint preliminary experiments, the Center for Disease Control and Prevention
(CDC), the University of Colorado and Aktiv-Dry have obtained promising results.
They have demonstrated that trehalose, or sucrose, or both, together with an
antioxidant, surfactant, and buffer, stabilize live virus measles vaccine during
carbon dioxide nebulization followed by drying. In the near future, formulation
packages and processing conditions will be optimized and coupled with
inexpensive powder delivery.
The opportunities for major advances in needle-free delivery of vaccines to save
lives are huge, and ancillary benefits may result from development of the AktivDry team’s simultaneous stabilization and micronization methods at temperatures
nearer ambient than in conventional spray drying or lyophilization. We are
determined to achieve convenient, safe, needle-free delivery of vaccines, and
cold chain elimination may also be within reach. We believe this technology can
be extended to other childhood vaccines, antibiotics, and anti-inflammatories.
The Aktiv-Dry team consists of a worldwide collaboration of publicly
funded research institutions and private pharmaceutical companies.
Collaborators on the Aktiv-Dry team include the University of Colorado, National
Jewish Medical and Research Center, the Serum Institute of India, BD
Technologies, as well as Johns Hopkins University, the University of Kansas, the
University of Maryland, and the Centers for Disease Control and Prevention
(CDC).
Aktiv-Dry will provide overall supervision, management, and coordination for the
duration of the five-year project. The principal investigator for this Grand
Challenges in Global Health initiative is Robert Sievers, Ph.D., co-founder AktivDry LLC, and a professor at the University of Colorado, Boulder campus. Brian
Quinn, Ph.D., MBA, and also co-founder of Aktiv-Dry, will be the project
manager.
Formulation of a stable dry power vaccine
Steve Cape, Ph.D., at CIRES on the CU-Boulder campus and Professors Mark
Hernandez, Ted Randolph, and Shelly Miller in the Engineering College, also on
CU’s Boulder campus, will conduct studies to formulate a thermally stable live
virus vaccine. The Aktiv-Dry team will attempt to stabilize live virus vaccine
powder that can be stored for several months without refrigeration. Such efforts
will be suitable for routine administration, mass distribution, and emergency
vaccination campaigns.
Similarly, development of stable dry powder formulation should serve as a
platform for administering mixtures of vaccines, even if each requires a different
pH or excipient combination for optimal stability. This should be feasible because
limited chemical or physical interactions are anticipated between particles of
heterogeneous nature stored together in a glassy state. The powders can be
stored together or separately and administered during the same vaccination
event.
Formulation improvements will be provided by the University of Colorado (both
Boulder and Denver campuses), University of Kansas (Lawrence), Aktiv-Dry
(Boulder), and Serum Institute of India (Pune, India).
In addition to developing a dry powder measles vaccine, the Aktiv-Dry team will
also design and fabricate an inexpensive, single-dose dispenser that delivers the
vaccine to the respiratory tract. Adaptations of BD’s dry powder inhaler
technologies and of an inexpensive device resembling a plastic tube will be
considered.
The estimated need for measles vaccine is 400 million doses per year. AktivDry’s target is a cost per dose of less than 25 cents for the vaccine powder and
delivery device.
The development and testing of the device will be provided by BD Technologies
(Research Triangle Park, NC), Aktiv-Dry, the University of Colorado, and Johns
Hopkins (Baltimore, MD).
Efficacy and safety of the new aerosol vaccine
Efficacy and safety assessments will be provided by Serum Institute of India,
CDC (Atlanta), National Jewish Medical and Research Center (Denver),
University of Maryland (Baltimore), and Johns Hopkins.
Using in vivo measurements, researchers at National Jewish, led by Kevin
Kisich, Ph.D., will improve efficacy and assess safety of the new aerosol vaccine.
Large clinical studies performed in Mexico have demonstrated that a live
attenuated measles vaccine delivered by an aerosolized wet mist safely provides
improved disease protection over that elicited by percutaneous injection.
However, because human subjects have not yet inhaled live attenuated measles
vaccine in a dry powder formulation, milestones have been created to confirm
safety in a series of sequential pre-clinical and clinical studies.
Dry powder inhalation of vaccine will be evaluated for safety in normal, healthy,
measles seropositive human volunteers supervised by Dr. Subhash Kapre and
his colleagues at the Serum Institute of India. If the vaccine is shown to be safe
in this population, the trials will be conducted in pediatric populations.
Serum Institute of India, which currently supplies most of the measles vaccine to
the developing world, will manufacture the vaccine powders. Milestones have
been scheduled to optimize a semi-continuous production capability of the bulk
particle formation process, and the transfer of this process to the manufacturing
plant in India.
The Aktiv-Dry team is extremely grateful to the Foundation for the National
Institutes of Health for the generous support to develop an inhalable measles
vaccine for the children in areas of the world that need the most support.
Aktiv-Dry Project Team
Aktiv-Dry LLC, Boulder, Colorado, www.aktiv-dry.com
BD Technologies, Research Triangle Park, North Carolina, www.BD.com
Center for Disease Control and Prevent, Atlanta, Georgia, www.cdc.gov
Johns Hopkins University, Baltimore, Maryland, www.hopkinsmedicine.org
University of Colorado, Boulder, Colorado, www.colorado.edu
University of Kansas, Lawrence, Kansas, www.pharmchem.ku.edu
University of Maryland (Baltimore County), www.umbc.edu
National Jewish Medical and Research Center, Denver, Colorado, www.njc.org
Serum Institute of India, Pune, India, www.seruminstitute.com
About Aktiv-Dry LLC
Aktiv-Dry LLC was founded in 2002 by University of Colorado Professors Robert
Sievers and John Carpenter, and by Brian Quinn, Ph.D., to develop life-saving
stable vaccines and pharmaceuticals for needle-free delivery. The company
currently engages in research and development projects for dry powder
applications and contracts with industrial, governmental, and not-for-profit clients.
For more information, contact 303-350-3060, and visit the Web site at
http://www.aktiv-dry.com.
About the Bill & Melinda Gates Foundation
The Bill & Melinda Gates Foundation works to promote greater equity in four
areas: global health, education, public libraries, and support for at-risk families in
Washington state and Oregon in the U.S. The Seattle-based foundation joins
local, national, and international partners to ensure that advances in these areas
reach those who need them most. The foundation is led by Bill Gates’ father,
William H. Gates Sr., and Patty Stonesifer, and has an endowment of
approximately $28 billion.
About the Foundation for the National Institutes of Health
The Foundation for the National Institutes of Health was established by the
United States Congress to support the mission of the National Institutes of Health
– improving health through scientific discovery. The Foundation identifies and
develops opportunities for innovative public-private partnerships involving
industry, academia, and the philanthropic community. A non-profit, 501(c)(3)
corporation, the Foundation raises private-sector funds for a broad portfolio of
unique programs that complement and enhance NIH priorities and activities.
On the Internet:
Grand Challenges in Global Health, www.grandchallengesgh.org
Bill & Melinda Gates Foundation, www.gatesfoundation.org
Foundation for the National Institutes of Health, www.fnih.org
Wellcome Trust, www.wellcome.ac.uk
Canadian Institutes of Health Research, www.cihr-irsc.gc.ca