May 30, 1997

Vaccine research helps children breathe easier

Vaccine research helps children breathe easier

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Jane Baker, R.N., B.S.N. (right), examines seven-month-old RSV patient Claw Howell while his mother, Suzanne keeps track of Clay's twin brother, Grant.

While everybody knows the minor-league misery of the common cold, some respiratory infections are considerably more ferocious, with influenza and respiratory syncytial virus (RSV) accounting for numerous hospitalizations and some deaths nationwide each year. Respiratory infections are among the most common types of illnesses in both children and adults.

VUMC researchers have been at the forefront in looking for vaccines for these more serious infections, said Dr. William C. Gruber, associate professor of Pediatrics.

³Something that Vanderbilt can be proud of is our efforts at understanding and combating these illnesses,² he said.

Exhibit A in Vanderbilt¹s effort is the work done here by Dr. Kathryn M. Edwards, professor of Pediatrics, and others, in developing a nasal spray influenza vaccine. That vaccine, which could be approved for widespread use as early as this summer, may even bring about a rethinking of the way flu immunizations are targeted, Gruber said.

Epidemiological studies show that there are about 20,000 deaths in an average year from influenza, mostly among older adults.

³The notion we¹ve had to come to grips with is that the primary focus is on older adults,² Gruber said. While concentrating on older adults targets the people who are most likely to have severe complications or death from influenza, it leaves out children, the portion of the population most likely to actually contract ‹ and therefore spread ‹ flu.

³We¹ve done very little in overall policy to impact the morbidity of flu,² Gruber noted. ³Targeting the vaccine to children may be the best strategy. We know that 20 to 40 percent of children get the flu in a given season, as opposed to 10 percent for adults.

"Children fuel flu epidemics. If you have school-age or pre-school age children in the home, you¹re more likely to get sick.²

But this strategy of limiting the spread of flu in everyone through limiting its spread among children has always faced a major roadblock ‹ it¹s very difficult to immunize children against influenza, because children, unlike adults, ordinarily require two shots with an interval in between, requiring two trips to the doctor.

It was this special challenge of immunizing children against the flu, coupled with the knowledge that a successful way of doing so would go far in slowing the yearly spread of the disease, that led VUMC researchers to pour their efforts into the creation of the attenuated nosedrop vaccine.

³We¹re coming to a time when we have a practical way to achieve immunity of all children,² Gruber said.


Respiratory syncytial virus (RSV), is a viral infection of the lower respiratory system and is a common cause of pneumonia and bronchiolitis in young children. The disease is characterized by wheezing, and commonly takes its greatest toll on children younger than six months of age.

³RSV is the single most common reason for children to be hospitalized,² Gruber said.

More than 200 children are admitted to Vanderbilt Children¹s Hospital every year with RSV, almost all of them during the winter months that are also the peak cold and flu season.

Most children, and most adults for that matter, carry antibodies to RSV, indicating that most people are often exposed to it, usually without it causing illness. The fact that the virus is all around is one of the reasons it is so hard to fight.

³The virus is ubiquitous. We are infected and re-infected over time. It is a formidable foe,² Gruber said.

Most vaccines against childhood diseases are given beginning several months after birth, because newborns don¹t have the range of immune response that even slightly older children have. That immaturity of immune response makes an RSV vaccine a difficult proposition, because the disease poses its greatest threat to babies under six months.

Currently, some immunity can be given to babies at especially high risk by giving them RSV antibodies in intravenous form monthly, but this is too unwieldy to be widely useful.

³Ultimately, a vaccine is the answer,² Gruber said. ³It should be given early and should last several months.²

Once again, VUMC is in the lead in working on a vaccine; Dr. Barney S. Graham, professor of Medicine, is conducting research on several aspects of RSV, including evaluating potential vaccines.

³To me, one of the most exciting things that¹s happened in RSV is that three industry groups now have active RSV programs,² he said. These industry groups ‹ pharmaceutical companies ‹ are funding research into several types of vaccines, including live vector, nucleic acids, and passive antibody.

³We¹ve also done human studies, where we¹ve tried to evaluate human immune responses,² Graham said. ³With that kind of activity going on, I¹m encouraged that we¹ll have a workable vaccine eventually.²

Dr. James E. Crowe Jr., instructor in Pediatrics, is conducting work on the neonatal immune system and its relationship to RSV, since a main obstacle to a successful vaccine is finding a way to stimulate the immature immune system of newborns.

There is also more basic, NIH-funded research going on in Graham¹s area, using a mouse model to study the pathogenesis of the disease.

RSV is everywhere. Seventy percent of babies are infected in their first year, and by age three, the infection rate is 100 percent. Yet only a small percentage react to the infection with the severe illness that leads to hospitalization.

³We¹re looking at viral causes and host causes as to why some react so severely,² Graham said. ³This has led to a lot of interesting collaboration for us, with Clinical Pharmacology, Pulmonary, NICU, and the Asthma Center.²