Randomized controlled trial of seroresponses to double dose and boaster influenza vaccination in frail elderly subjects

Responses to influenza vaccination are poor in frail elderly subjects who s uffer the greatest morbidity and mortality due to infection. Therefore, a r andomized clinical trial was performed to determine the effect of a double dose and booster vaccination on antibody responses after influenza vaccinat ion. A total of 815 patients (median age 83 years, median disability score 8, median disease categories 2 and median number of medications 4) residing in 14 nursing homes in the Netherlands were vaccinated during the influenz a season 1997-98. The first vaccine dose (15 or 30 mug) was given on Day 0 followed by a booster dose (placebo or 15 mug) on Day 84. Blood samples wer e taken before and 25 days after vaccination. There were four treatment gro ups: (i) 15 mug and placebo, (ii) 15 mug and 15 mug booster, (iii) 30 mug a nd placebo and (iv) 30 mug and 15 mug booster. Geometric mean antibody tite rs of those receiving the double vaccine dose was 15% (95% CI, 6% to 24%, P = 0.001) higher as compared to the standard 15 mug dose. A booster dose, g iven 84 days after the first vaccination, yielded postvaccination titters t hat were 14% (95% CI, 9% to 19%, P = 0.001) higher as compared to placebo. !jubgroup analysis did not reveal patient groups that had a proportionally greater benefit from adapted vaccination strategies. It is concluded that h igher antibody responses can be achieved in frail elderly people by a doubl e vaccine dose or a booster vaccination. (C) 2001 Wiley-Liss, Inc.