An experimental nasal spray flu vaccine protected young children against an influenza strain not covered by the vaccine, according to results from the second year of a study supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the vaccine manufacturer. Details appear in the February issue of the Journal of Pediatrics.
In an unexpected twist, during the 1997-98 flu season when the study took place, the predominant circulating flu virus was A/Sydney. Since this strain had not emerged as an upcoming threat when the vaccine was made, the vaccine was not designed to protect against it. Yet the nasal spray vaccine proved 86 percent effective against A/Sydney. In addition, none of the children became infected with the three strains of influenza the vaccine was specifically designed to prevent.
"This study gave us an unanticipated opportunity to test how well this vaccine works against a variant virus, an influenza strain that had undergone so-called 'antigenic drift,'" says Linda Lambert, Ph.D., influenza program officer at NIAID. "Virus proteins important to disease development," she explains, "had undergone minor, spontaneous changes. Still, the vaccine performed remarkably well in this 'natural experiment.'"
The double-blind, placebo-controlled trial enrolled 1,358 children between 2 and 7 years old. These children had entered the vaccine study during the 1996-97 flu season and returned for a single revaccination during the 1997-98 flu season. Each participant received either the nasal spray vaccine, FluMist(tm), or placebo, matching what they had received the previous year. Those who got FluMist(tm) experienced no serious side effects related to vaccination.
Of the 71 cases of influenza seen in the study children, 66 were caused by A/Sydney. Only 15 of the A/Sydney cases occurred among the 917 children who got FluMist(tm). These 15 children had significantly milder disease symptoms -- shorter duration of fever, fewer cases of influenza-related middle-ear infections, and no lower respiratory tract disease -- than did the 51 placebo recipients who developed A/Sydney flu. All five cases of non-A/Sydney flu occurred among the 441 children in the placebo group.
The first-year study results -- which showed an overall efficacy of 93 percent during the 1996-97 flu season when the circulating influenza strains were well-matched to the vaccine -- were published in The New England Journal of Medicine in May 1998.
"In the second year of this study, the safety and efficacy results were very similar to those seen in year one," says Robert Belshe, M.D., study chair and director of the Center for Vaccine Development at Saint Louis University. "The overall protection rate for the two-year period was 92 percent. The additional data on cross-protection against A/Sydney and significant reduction in disease severity among the vaccinees are extremely important new pieces of information from year two." The second-year data also found that the vaccine provided 94 percent protection against influenza-related middle-ear infections, or otitis media. Otitis media is the most common illness in young children requiring a doctor visit. Since the licensed flu vaccine was not included in the study, no head-to-head comparison between it and FluMist(tm) can be made.
The trial took place at 10 clinical sites nationwide, including six Vaccine and Treatment Evaluation Units funded by NIAID and four sites funded by the vaccine manufacturer, Aviron.
An estimated 35 to 50 million Americans come down with influenza each flu season, which typically lasts from November to March. Children are two to three times more likely than adults to become ill with flu, and children frequently spread the virus to others. Although most people recover from the illness, influenza's deadly potential among vulnerable populations is often underestimated, and at least 20,000 people in the United States die from influenza and its complications each year.
NIAID has supported the development of this "cold-adapted" live virus influenza vaccine concept for nearly 25 years. Early work by researchers in NIAID's Laboratory of Infectious Diseases and their colleagues at the University of Michigan paved the way. They developed weakened influenza viruses that could stimulate immunity in the cooler nasal passages but could not cause disease in the warmer temperatures of the lower airways. Simpler versions of FluMist(tm) were tested by NIAID-supported researchers in smaller trials. Then in 1995,
Aviron entered into a Cooperative Research and Development Agreement with NIAID for development of an advanced version of the vaccine into a commercial product.
Aviron is a biopharmaceutical company based in Mountain View, CA, focused on the development of live virus vaccines to prevent disease.
NIAID is a component of the National Institute of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
RB Belshe, et al. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatrics 136:168-75 (2000).
K Subbarao. As good as the real thing. J Pediatrics 136:139-41 (2000).
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Materials provided by National Institute Of Allergy And Infectious Diseases. Note: Content may be edited for style and length.
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