and John C. Victor, Ph.D., M.P.H. Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines Arnold S. Monto, M.D., Suzanne E. Ohmit, Dr.P.H., Joshua G. Petrie, M.P.H., Emileigh Johnson, B.S., Rachel Truscon, M.P.H., Esther Teich, M.A., Judy Rotthoff, R.N., Matthew Boulton, M.D., M.P.H., and John C. Victor, Ph.D., M.P.H. N Engl J Med 2009;361:1260-7 R3 Hyun Jin Park/Prof. Mi Suk Lee

Backgrounds Types of vaccine for the prevention of seasonal influenza 1. Inactivated vaccine : Containing killed or inactivated organisms with heat or chemicals 2. Live attenuated vaccine : Prepared from live microorganisms that have lost their virulence Trivalent influenza vaccine Two different influenza type A strains + 1 influenza type B strain Formulated annually, based on prevalent influenza strains Injection or intranasal administration The factors affecting to efficacy of vaccines Age and health of the vaccine recipients Extent of antigenic similarity between the strains

Live attenuated vaccine Objective Inactivated vaccine Live attenuated vaccine ? 1. Absolute Efficacy? 2. Relative Efficacy? 2007-2008 Viral culture PCR assay

Methods – Study design, objectives and used vaccine Randomized, double-blind, placebo-controlled, community-based trial A 4-year period, beginning in 2004 Objetives Primary objective : the absolute efficacy Secondary objective : the relative efficacy Vaccine products Inactivated vaccine Fluzone, Sanofi Pasteur, 0.5-ml dose containing 15 μg of hemagglutinin Live attenuated vaccine FluMist, MedImmune, 0.2-ml dose containing 10 fluorescent focus units Assortant virus strains A/Solomon Islands/3/2006 (H1N1) A/Wisconsin/67/2005(H3N2) B/Malaysia/2506/2004 (B/Victoria lineage)

Methods – Enrollment, Randomization, and follow up Healthy men and women 18 to 49 years of age Four university campuses in Michigan Randomized, Double-blind study Inactivated vaccine IM : placebo IM = 5:1 Live attenuated vaccine : placebo intranasal spray = 5:1 Follow up Diary cards listing possible reactions and fill out each day for 7 days From November 2007 through April 2008, 2 or more respiratory or systemic symptoms : Collection of specimens by throat swabs Symptomatic influenza The primary end point : Case of symptomatic illness + influenza A or B by viral culture or a real-time PCR assay

Results - Participants

Results Reported Reactions Serious Adverse Events Arm soreness : only local and systemic reactions Inactivated vaccine : Placebo = 52.6% : 21.3% Runny nose or congestion Live attenuated vaccine : Placebo = 52.3% : 37.7% Serious Adverse Events Only 1 serious adverse event within the first 30 days Hospitalization for depression and anxiety in a recipient of intranasal placebo (Unrelated to the intervention) 14 additional serious adverse events within 6 months 8 in inactivated vaccine 4 in live attenuated vaccine 2 in intranasal placebo

Results

Influenza A 108 pts + Influenza B 11 pts Results Total 119 pts= Influenza A 108 pts + Influenza B 11 pts

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