麻豆影院

Professor Bob Sievers started out studying moon dust as part of NASA鈥檚 Apollo lunar analysis program. Today he鈥檚 turning vaccines into tiny dust-like particles to save millions of lives and decimate deadly diseases.

Measles is sitting firmly in Sievers鈥� vision, with the potential to add vaccinations for human papillomavirus (HPV) and influenza to his arsenal in the foreseeable future. The CU-麻豆影院 chemistry and biochemistry professor and his team have devised a new vaccine formulation that makes it possible for patients to inhale vaccine microparticles instead of being injected.

They鈥檝e also created the PuffHaler鈩�, a cheap, disposable and easily transportable device to administer single-dose vaccines by forming an aerosol to inhale. It鈥檚 a technological one-two punch that could knock out needles to vaccinate for measles and other diseases.

Facing a resurgence of measles

The World Health Organization reports vaccination has prevented an estimated 4.3 million measles deaths in less than a decade. Worldwide, measles deaths fell by 78 percent between 2000 and 2008 (from an estimated 733,000 annually to 164,000), and most regions have achieved United Nations goals of reducing measles mortality by 90 percent as of 2010.

But Southeast Asia and increasingly Africa are falling short. India accounts for nearly two-thirds of global measles deaths in children and infants, and 10 percent of India鈥檚 preschool-aged deaths are measles-related. WHO Director-General Dr. Margaret Chan notes 鈥渟igns of stalling momentum鈥� and warns of a resurgence of this highly contagious disease if vaccination efforts are not sustained.

When the Bill and Melinda Gates Foundation announced the Grand Challenges in Global Health six years ago, a significant source of funding emerged to tackle major obstacles in children鈥檚 and women鈥檚 health care worldwide. Administering needle-free drugs and eliminating the need for refrigeration were two key missions of the challenge that helped fund Sievers鈥� $20 million inhalable vaccine research effort.

Pending government approvals, the inhalable vaccine is slated for Phase I clinical trials later this year with the Serum Institute in India, the world鈥檚 largest producer of vaccines.

鈥淗e鈥檚 done a remarkable job advancing into the clinical phase,鈥� says Michael Gottlieb, associate director of science and deputy director of the Grand Challenges in Global Health initiative for the Foundation for the National Institutes of Health, which has directly managed 20 of these grants, including Sievers鈥�. 鈥淚t has tremendous implications . . . It鈥檚 remarkable to get this far in a relatively short period of time. Many of the grants were more upstream research.鈥�

After clinical trials, Gottlieb says the next hurdle will be influencing government and international aid organization policy decisions and their commitment to get an inhalable vaccine on the ground.

鈥淚n a poor country you try to recycle everything, just as we once did here,鈥� Sievers says. 鈥淯nfortunately, that includes needles.鈥�

Eliminating needles has the potential to diminish everything from hepatitis and AIDS to cultural, educational and environmental barriers to vaccination.

To abandon needles, Sievers鈥� team created tiny particles mixed with sugars and amino acids that are both stable and capable of being dispensed through a small puff of air that is inhaled into the lungs from an antistatic plastic bag. Low cost was also imperative: A dose costs no more than 17 cents, which goes toward the vaccine itself, and the delivery device only costs 10 cents. Most of the system is disposable.

鈥淭his also is a logistics advance,鈥� Sievers says. 鈥淚t鈥檚 an accident of history that we use rather primitive methods 鈥� puncturing flesh 鈥� to administer vaccines.鈥�

Time and temperature

The key was being able to create particles that were five microns in diameter or smaller 鈥� about the size of a human red blood cell, or about one-tenth the thickness of a fine strand of human hair.

Currently, vaccines are shipped as 鈥渃akes,鈥� small pellets that travel around the developing world in ice chests and have to be mixed with purified water. Then they must be used within six hours. That鈥檚 six hours for bacteria to grow as the needle goes in and out of the solution amid hot, humid weather.

Sievers鈥� plan has many advantages. The likelihood of contamination is drastically reduced with single-dose packaging, as is the wastage 鈥� vaccines destroyed because of the probability of spoiling. Last year, 400 million doses of measles vaccine were sold in 127 countries. Forty percent of it was wasted because not enough people showed up during a day to use up all the doses mixed in the morning.

鈥淭emperature and time are your enemies. Moisture, too,鈥� Sievers says.

The inhalable vaccine is dried under clean conditions, so there are fewer chances for bacterial growth, and there is a lower risk for infection because there is no piercing of the skin.

Now the findings of Sievers and an international team of about 25 scientists, engineers and physicians whom he led as a principal investigator were published by the聽Proceedings of the National Academy of Sciences聽in the Jan. 31, 2011, issue. The team鈥檚 paper, co-authored by Sievers, CU lab manager聽Stephen Cape聽(MChemEngr鈥�97, PhD鈥�00), scientists from Johns Hopkins University, Centers for Disease Control and Prevention and others, describes the first successful inhalable dry powder vaccine for protection against measles in Rhesus macaques.

鈥淚 work in a very applied and interdisciplinary area,鈥� Sievers says. 鈥淭his paper is a beautiful example of that.鈥�

A measles-free world

Sievers says his scientific interests over the years have been guided by a commitment to pursue socially relevant projects leading to a better environment. Moon dust led to aerosol studies where he looked at atmospheric chemistry and the effects of inhaling pollutants.

When he started noticing the pharmaceutical industry showing up at meetings alongside atmospheric scientists, he crossed into the medical field. With CU鈥檚 blessing, Sievers has since founded a private spinoff company called Aktiv-Dry LLC to develop needle-free vaccine delivery systems and new formulations of stable vaccines, antivirals and antibiotics.

All of this was a natural progression for Sievers who served as a CU regent from 1990 to 2002, during which time he helped acquire the closed Fitzsimons Army Base for CU鈥檚 new medical school. He also directed the CU Cooperative Institute for Research in Environmental Sciences (CIRES) for 13 years. CIRES researchers focus on innovation and collaboration in studying all aspects of the Earth and how natural and human-made disturbances impact a changing planet. With the Sievers team moving into new research areas, CIRES added a global health program to its scope of studies.

It鈥檚 a legacy not lost on co-author Cape who has worked with Sievers since 2002. Cape personally reformulated the vaccine that was tested on the Rhesus macaques, but he hadn鈥檛 originally envisioned his career taking a global health trajectory.

鈥淚 really enjoy the mission 鈥� that focus on meeting the needs of those who aren鈥檛 able to help them themselves,鈥� Cape says, noting the advantages of working with someone who is a scientist, a successful entrepreneur and a solid friend. Ever the Renaissance man, Sievers鈥� art even looms outside Cape鈥檚 lab window 鈥� a giant red obelisk marble sculpture on the Norlin Quad.

鈥淗e鈥檚 definitely someone with big picture ideas,鈥� Cape says, emphasizing the gratification of tedious day-to-day tasks overridden by a larger mission. 鈥淓ven without the profit margin, saving hundreds of thousands of children鈥檚 lives is inspiring.鈥�

One great hope is that eventually people might be able to administer this vaccine to babies younger than nine months because many are infected and die before they are vaccinated.

They are not writing on a blank slate. In 1989, during a measles outbreak in Mexico, the government took emergency measures to vaccinate nearly three million children using a wet mist made with an air compressor available at local hardware stores. It was a crisis, and no one kept meticulous records, but there hasn鈥檛 been another major measles epidemic in Mexico since then. It鈥檚 anecdotal, but it gives Sievers hope.

鈥淭his could save lives. We lose, just due to measles, several hundred people a day,鈥� Sievers says. 鈥淥ur dream is a measles-free world, and that could happen if the vaccine coverage is sufficient.鈥�

That would require vaccinating about 90 percent of a population for 鈥渉erd immunity鈥� or nearly 100 percent for eradication. But with the ease of the new inhalable measles vaccine system he says he would expect coverage to become a lot better.

鈥淵ou don鈥檛 have to be good enough to give a shot,鈥� Sievers says. 鈥淎nybody could give this 鈥� just breathe from a bag.鈥�

Jennie Lay聽(MJour鈥�05) is a freelance journalist based in Steamboat Springs.

Photo by Glenn Asakawa聽