A prospective, randomized, open-label trial comparing the safety and efficacy of trivalent live attenuated and inactivated influenza vaccines in adults 60 years of age and older

Background: Although influenza is a major public health concern among adults >= 60 years of age, few large, prospective studies of influenza vaccines have been conducted in this population. The goal of the present study was to directly compare the safety and efficacy of LAIV and TIV in adults >= 60 years of age. Materials and methods: A prospective, randomized, open-label, multicenter trial was conducted in South Africa. In March-April 2002, 3009 community-dwelling ambulatory adults 60-95 years of age were randomized 1:1 to receive a single dose of LAIV or TIV. Surveillance for influenza illness was conducted through November. Serum antibody titers were evaluated in all participants, and interferon-gamma enzyme-linked immunosorbent spot assay responses were evaluated in a cohort of subjects. Solicited reactogenicity and adverse events were monitored for days 0-10 postvaccination; serious adverse events were monitored for the entire study. Results: Influenza illness caused by vaccine-matched strains was detected in 0.8% (12/1494) and 0.5% (8/1488) of LAIV and TIV recipients, respectively; the relative efficacy of LAIV vs TIV was -49% (95% Cl: -259, 35). As expected, greater serum antibody responses were seen with TIV, and greater cellular responses were seen with LAIV (although not for influenza B). Among subjects with culture-confirmed influenza illness, post hoc analyses revealed trends toward less feverishness (LAW, 14%; TIV, 46%; P = 0.05) and less fever (LAIV, 9%; TIV, 31%; P=0.16) among LAIV recipients. In each treatment group, 38-39% and 24-25% of subjects had baseline hemagglutination inhibition titers of <= 4 for A/H1 and A/H3, but 7 of 8 TIV cases and 7 of 12 LAIV cases of matched-strain influenza occurred among these subjects. Runny nose/nasal congestion (+13%), cough (+5%), sore throat (+5%), lethargy (+3%), and decreased appetite (+2%) were reported by more LAIV vs TIV recipients. Injection site reactions were reported by 27% of TIV recipients. SAEs were reported by a similar proportion of LAIV and TIV recipients (9% vs 8%). Conclusions: Given the low incidence of influenza in both groups, no conclusions were possible regarding the relative efficacy of LAIV and TIV. There was a trend toward less feverishness/fever among LAIV recipients who developed influenza compared with TIV recipients with influenza, consistent with results from studies comparing the vaccines in children. A disproportionate number of influenza illnesses occurred among baseline seronegative subjects, particularly for those receiving TIV, which suggests that this subgroup has the greatest need for improved influenza vaccination. The safety profiles of LAIV and TIV were consistent with results from previous studies in older adults and no significant safety concerns were identified. clinicaltrials.gov identifier, NCT00192413. (C) 2011 Elsevier Ltd. All rights reserved.