1. 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

2. 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

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

4. 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)

5. 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

6. Results - Participants

7. 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

8. Results

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

10. 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.