The data were presented here at the 38th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy by lead investigator Robert Belshe, MD, director of infectious diseases and immunology, and director of the Center for Vaccine Development at Saint Louis University, St. Louis, Mo.
The trial was conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID).
Although it provided some protection against it, the influenza A/Nanchang/933/94, rather than the influenza A/Sydney strain, was included in the 1997-98 formulation because FluMist was designed to match the flu shot marketed that year. The flu shot was not studied in this trial, according to a statement from the manufacturer.
"Live-attenuated virus vaccines such as FluMist are thought to mimic natural infection better than other types of vaccines. In addition, FluMist is delivered to the upper airway, the natural port of entry for the influenza virus," Belshe said.
Only 2% of children vaccinated with FluMist (15 out of 917) experienced culture-confirmed influenza, all of which was attributable to the A/Sydney strain, while 13% of the placebo recipients (56 of 441) experienced culture-confirmed influenza.
The difference between these two influenza attack rates is used to calculate the overall protection rate of 87%. The incidence of pneumonia and other lower respiratory diseases was also reduced, compared with placebo. Eight children in the placebo group developed influenza-related wheezing, bronchitis or pneumonia. All of these were due to the A/Sydney strain. No children who received FluMist experienced lower respiratory complications.
These new data are from the second year of a randomized, placebo-controlled study in healthy children initiated during the 1996-97 flu season. The children were invited back to participate for a second flu season in the 1997-98 follow-up trial. They were either vaccinated with a single dose of FluMist or a placebo spray. Of the 15 children out of 917 children in the FluMist group who did contract influenza, the illness appeared to be milder than in the control group, based on frequency of complications and duration of fever.
"Considering the unexpected emergence and severity of the A/Sydney strain during last year's flu season, we believe the observed level of protection is especially important," said J. Leighton Read, MD, chairman and chief executive officer of Aviron. "It confirms the results we have seen in the past and indicates that FluMist may provide protection against strains of influenza somewhat different from those in the annual formulation."
The vaccine formulation is updated each year to include the most current influenza virus strains. The Centers for Disease Control and Prevention (CDC), the World Health Organization, and the Food and Drug Administration (FDA) determine which three strains of the influenza virus are likely to infect the population in the coming flu season.
Reports published in the CDC's Morbidity and Mortality Weekly Report indicate that there were numerous outbreaks last year of influenza A/Sydney strain, a variant of one of the strains included in the vaccine. Influenza A/Sydney was not included in the 1997-98 vaccine, and these reports indicate the protection provided against this strain by the vaccine may have been low.
Results from the year-one study (1996-97 flu season) published in the May 14 New England Journal of Medicine, showed that only 1% (14 of 1,070) of the children who received FluMist developed culture-confirmed influenza, vs. 18% (95 of 532) of the children who received placebo - a protection rate of 93%. The first year data also indicated that the vaccine provided 98% protection against influenza-associated otitis media.
This trial was conducted under a Collaborative Research and Development Agreement between Aviron and the NIAID. The trial involved 10 sites nationwide.
Editor's note: The request for additional data by the FDA is not unreasonable. It is one thing to produce an experimental vaccine for a few thousand subjects. It is another to produce one to be used in multiple offices for millions of people. Let's get it right! It is an important product. - P. Brunell, MD