More than a bottle of medicine
For a vaccine to be effective, the strategy behind it has to work
By Pam Auchmutey
Orenstein's epiphany occurred in 1974. It happened in India, where
he was sent to help eradicate smallpox after joining the CDC as an Epidemic
Intelligence Service officer.
changed my life," says Orenstein. "I saw this
terrible, disfiguring disease with a high mortality disappear before my eyes because of a vaccine. It lured me to the power and potential of vaccines. It also taught me that just having the vaccine in the bottle isn't enough. There's a science that goes beyond merely having an effective vaccine to get the desired impact on disease."
Orenstein's work—formerly as director of the CDC's National Immunization Program and now as director of vaccine policy and development for the Emory Vaccine Center—revolves around that premise. Such was the case with smallpox. The vaccine worked because the strategy to halt disease transmission—surveillance and containment—succeeded. "It illustrated the power of the vaccine and using the right strategy to deliver it," he says.
Orenstein understands such lessons well, having led the CDC's $1.6 billion effort to reduce vaccine-preventable diseases worldwide and helping create the blueprint for the nation's childhood immunization program. Today, he is applying lessons learned to help advance scientific discovery at the Emory Vaccine Center and to address the challenges related to vaccine development, manufacture, delivery, financing, and policy.
More than ever, his utmost concern is influenza and the very real possibility of a flu pandemic. The key to prevention, says Orenstein, is "to determine whether a policy emphasizing vaccination of children, who are major transmitters of influenza viruses, would have greater benefit than the current strategy, which focuses on people like the elderly, who are at risk of complications and who frequently don't have good immune responses."
Orenstein is tackling the flu vaccine question with medicine, nursing, and public health researchers at Emory. In one study, experts are gathering opinions from physicians, parents, insurers, manufacturers, and others to determine the feasibility of a policy requiring annual vaccination of the U.S. population against influenza. In another study, experts are seeking to determine the best method for flu immunization delivery.
"We've been working with the state of Georgia and public and private providers to look at whether they offer flu vaccine through special clinics, walk-in clinics, or by appointment," Orenstein says. "We want to determine what kinds of practices are associated with better coverage so we can set standards for what works best."
He is also seeking to improve flu vaccination rates among health care workers at Emory and Atlanta hospitals. "Health care workers often have the same misconceptions and fears about vaccines as the public," he says. "We are working with hospitals to determine their vaccination policies, how successful they've been, and which policies are associated with higher coverage levels. We'd like to achieve better coverage than the 40% average for health care workers in the country."
The Emory Vaccine Center has afforded Orenstein opportunities to address diseases beyond the scope of his CDC work. HIV tops the list. In a five-year study funded by NIH, investigators from Emory, the University of Pennsylvania, Georgia Tech, and Duke are working to genetically engineer a specific vector, modified vaccinia ankara or MVA, which carries HIV genes, to induce a better immune response than other MVA vectors now in clinical trial. The goal of the study is to take this new MVA HIV vaccine from the laboratory into development and eventual clinical trial to demonstrate that it safely induces an immune response that can prevent AIDS.
At the Hope Clinic, the clinical trial arm of the Emory Vaccine Center, investigators are looking at ways to prevent viscerotropic disease, a rare but severe reaction to the vaccine for yellow fever. They are giving yellow fever vaccine in combination with immunoglobulin, which contains protein antibodies that attach to the virus. They hope the combination will reduce the amount of virus in the blood to levels easier for the body to control and thereby reduce risk of developing viscerotropic disease.
Hope Clinic study could set the stage for delivering vaccines through the
skin. Orenstein's collaborators are using a technique to clean the
skin that also removes the stratum corneum, the layer that inhibits access
to dendritic cells. These cells help generate an immune response in the
body. If successful, this technique could deliver vaccines more effectively,
eliminate syringes, and provide more doses from the same amount of vaccine.
In the policy arena, Orenstein serves on a working group with the National Vaccine Advisory Committee to look at the financing of vaccines, especially those for children. Given the large number of vaccines recently incorporated into the child and adolescent immunization schedule, the cost to buy vaccines for children has risen substantially. In 1987, the price to purchase vaccine doses for eight diseases was $116 per child. Today, vaccines for 16 diseases cost $1,700 per child.
"This tremendous change accounts for the cost increase," says Orenstein. "But having new vaccines available and recommendations to use them are not sufficient to reduce disease burdens if doctors can't afford to give them, or parents can't afford to buy them, or insurance policies don't cover them, or the government is not purchasing vaccines for people the same as before. These issues need to be solved to obtain the same level of control with new vaccines and recommendations as we did with the old."
In the eyes of others, the former CDC administrator carries a lot of clout when it comes to vaccine policy. "Walt has the ability to collect information, analyze it, and then make recommendations that will be listened to and followed in this country and around the world," says School of Medicine Dean Thomas Lawley.
A case in point was the "Universal Vaccination Against Influenza: Are We Ready?" meeting in 2005. Emory's Exploratory Center for Interdisciplinary Research in Vaccinology co-sponsored the meeting with the CDC and the National Vaccine Program Office.
"One result that came out of that meeting was a consensus to move toward a universal vaccination approach for the country," says Orenstein. "The logical first group was children 24 to 59 months of age, and that became national policy."
Participants came to that conclusion based on evidence that showed young children have a significant health burden in terms of doctor's visits and ER visits for flu. These children also transmit the flu to others.
When it comes to developing vaccine policy, "showing community benefits as a result of decreased disease transmission is not enough," says Orenstein. "There must be individual benefits as well. You can't just say, ‘Let's get Johnny vaccinated to protect grandma.' That may make sense to us as health professionals. But parents aren't willing to do that unless they feel the vaccine is very safe and Johnny is getting some benefit."
This spring, Orenstein took on another role in the Center for Influenza Research and Surveillance, one of six new national centers funded by NIH. Researchers from the School of Medicine and the University of Georgia's veterinary school will investigate how flu viruses adapt to new hosts and how they are transmitted between hosts. Their primary goal: to determine how flu viruses mutate to infect other species—especially humans infected with the avian flu virus—in order to prevent a possible flu pandemic.
Copyright © Emory University, 2007. All Rights Reserved