March 2000
BETHESDA, MD - An experimental nasal spray influenza vaccine (FluMist, Aviron/Wyeth Lederle) protected young children against an influenza strain not covered by the vaccine, according to results from a recent study.
In an unexpected twist, during the 1997-98 flu season when the study took place, the predominant circulating virus was influenza 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% 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, according to the study published recently in the Journal of Pediatrics.
"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,'" said Linda Lambert, PhD, influenza program officer at National Institute of Allergy and Infectious Diseases (NIAID). "Virus proteins important to disease development had undergone minor, spontaneous changes. Still, the vaccine performed remarkably well in this `natural experiment.'"
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The double-blind,
placebo-controlled trial enrolled 1,358 children between 2 and 7 years old.
These children 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 cold-adapted live-virus nasal influenza
vaccine, or placebo, matching what they had received the previous year. Those
who got the cold-adapted vaccine experienced no serious side effects related to
vaccination, according to the study results.
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 received the nasal spray vaccine. 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 showed an overall efficacy of 93% during the 1996-97 flu season when the circulating influenza strains were well-matched to the vaccine.
"In the second year of this study, the safety and efficacy results were very similar to those seen in year one," said Robert Belshe, MD, study chairman and director of the Center for Vaccine Development at Saint Louis University, St. Louis, MO. "The overall protection rate for the two-year period was 92%. 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% protection against influenza-related otitis media, which is the most common illness in young children requiring a doctor visit. Since the licensed influenza vaccine was not included in the study, no head-to-head comparison between it and FluMist 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.
NIAID has supported the development of this cold-adapted live virus influenza vaccine concept for nearly 25 years. The cold-adapted vaccine is based on early studies that showed weakened influenza viruses could stimulate immunity in the cooler nasal passages but could not cause disease in the warmer temperatures of the lower airways.
For more information:
- Belshe RB, Gruber WC, Mendelman PM, 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.2000;136:168-75.
- K Subbarao. As good as the real thing. J Pediatrics 2000;136:139-41.
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