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A Randomized Controlled Trial

Kristin L. Nichol, MD, MPH; Paul M. Mendelman, MD; Kenneth P. Mallon, MS, MHS; Lisa A. Jackson, MD, MPH; Geoffrey J. Gorse, MD; Robert B. Belshe, MD; W. Paul Glezen, MD; Janet Wittes, PhD; for the Live Attenuated Influenza Virus Vaccine in Healthy Adults Trial Group

JAMA. 1999;282:137-144.

Context  Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.

Objective  To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults.

Design  Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998.

Setting  Thirteen centers across the United States.

Participants  A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population.

Intervention  Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n=3041) or placebo (n=1520) in the fall of 1997.

Main Outcome Measures  Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events.

Results  Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain.

Conclusion  Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.

Author Affiliations: Medicine Service, VA Medical Center, and the University of Minnesota, Minneapolis (Dr Nichol); Aviron, Mountain View, Calif (Dr Mendelman and Mr Mallon); Immunization Studies Program, Center for Health Studies, Group Health Cooperative and Department of Epidemiology, University of Washington, Seattle (Dr Jackson); Medicine Service, VA Medical Center (Dr Gorse), and Department of Medicine, St Louis University (Drs Gorse and Belshe), St Louis, Mo; Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Tex (Dr Glezen); and Statistics Collaborative, Washington, DC (Dr Wittes).

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