A randomized placebo-controlled double-blind trial of a nasally administered inactivated trivalent influenza vaccine formulated with partially purified meningococcal outer membrane proteins (OMP-TIV) was conducted in 1349 healthy adults aged 18-64 years. Subjects received either vaccine containing 15 μg of haemagglutinin (HA) of each of three influenza strains for the 2003-2004 season on days 0 and 14, or 30 μg on day 0 and saline placebo on day 14, or placebo on days 0 and 14. Vaccination was well tolerated, with similar reactogenicity as placebo. Compared to placebo, statistically significant increases in mean serum haemagglutinin inhibition reciprocal titers and salivary secretory IgA to all 3 antigens were seen on day 28 for both vaccine dose groups. The incidence of culture-positive influenza and fever >37.8°C and cough and one or more of sore throat, runny nose or nasal congestion, muscle or joint ache, headache, fatigue, or chills or culture positive influenza and at least two of these symptoms was low (16/1349; 1.2%). In the intent-to-immunize population too few febrile culture-confirmed illness events (n=4) occurred to perform analysis. Fever occurred infrequently, even in the presence of positive cultures and disabling multi-symptom disease. In participants receiving all doses of either vaccine regimen the incidence of culture-confirmed influenza with respiratory symptoms and with or without fever was 0.77% (7/904) vs. 2.03% (9/443) in placebo recipients (p=0.045, Fisher's exact test; relative risk reduction 62%), despite circulation of a drift variant A/H3N2 that was poorly matched to vaccine. An OMP-TIV vaccine was well tolerated and reduced risk of symptomatic culture confirmed influenza. Vaccine efficacy will need to be validated in a season with a higher attack rate.
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