Live Attenuated Flu Vaccine May Be Less Effective Than Inactivated Flu Vaccine

Laurie Barclay, MD

September 24, 2009

September 24, 2009 — During the 2007–2008 flu season, the inactivated influenza vaccine (injection) was more effective than the live attenuated vaccine (intranasal spray) in preventing laboratory-confirmed symptomatic influenza A (mostly H3N2) in healthy adults. However, both vaccines prevented influenza illnesses, according to the results of a randomized, double-blind, placebo-controlled trial reported in the September 24 issue of the New England Journal of Medicine.

"The efficacy of influenza vaccines may vary from year to year, depending on a variety of factors, and may differ for inactivated and live attenuated vaccines," write Arnold S. Monto, MD, from the University of Michigan School of Public Health in Ann Arbor, and colleagues. "Influenza-related morbidity was high in 2007–2008, a year in which type A (H3N2) viruses predominated; these viruses were characterized by a slight antigenic drift from the type A (H3N2) viral strain included in the vaccine."

This trial compared the estimated absolute and relative efficacies of licensed inactivated and live attenuated influenza vaccines in 1952 healthy adults who received study vaccines in the fall of 2007. Influenza activity was documented from January through April 2008, with influenza types A (H3N2) accounting for about 90% of circulating virus and type B for about 9%.

Absolute efficacy was determined by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both. For the inactivated vaccine, absolute efficacy was 68% (95% confidence interval [CI], 46% – 81%) compared with 36% (95% CI, 0% – 59%) for the live attenuated vaccine. Estimates of relative efficacy showed that for participants who received inactivated vaccine there was a 50% (95% CI, 20% – 69%) reduction in laboratory-confirmed influenza compared with those who received live attenuated vaccine.

Against the influenza A virus, absolute efficacy was 72% (95% CI, 49% – 84%) for the inactivated vaccine and 29% (95% CI, −14% to 55%) for the live attenuated vaccine, yielding a relative efficacy of 60% (95% CI, 33% – 77%) for the inactivated vaccine.

"In the 2007–2008 season, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic influenza A (predominately H3N2) in healthy adults," the study authors write. "The live attenuated vaccine also prevented influenza illnesses but was less efficacious."

Limitations of this study include lack of conclusive evidence to date regarding the efficacy of the 2 vaccines for the influenza B viruses.

"We are entering a new era of influenza control, one in which different types of vaccines may be appropriate for different age groups," the study authors conclude. "In preliminary testing of prevaccination and postvaccination serum samples collected as part of the current study, a small proportion of the participants who received the inactivated vaccine in the fall of 2007 had antibody responses to the novel virus, but none of the recipients of the live attenuated vaccine had a similar response. Ideally, data from direct comparison of the vaccines will be made available to inform the choices that will be required as we go forward into relatively uncharted territory."

Dr. Monto has disclosed receiving consulting fees from GlaxoSmithKline, Novartis, and Baxter; lecture fees from Sanofi Pasteur and GlaxoSmithKline; and grant support from Sanofi Pasteur. Six other study authors have disclosed receiving grant support from Sanofi Pasteur.

N Engl J Med. 2009;361:1260–1267.

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