Through test negative designs for visiting a doctor because of influenza-like illness, many studies have found decreasing efficacy of repeated vaccination. Furthermore, waning effectiveness during interseason periods has been reported. This study was conducted to confirm negative effects of repeated vaccination in individuals with the same vaccine strain and to measure waning effects.
Our cohort includes 66 participants older than 65 years old recruited from an outpatient department of one hospital. All were vaccinated, with hemagglutination inhibition (HI) antibody titers measured from 2001/02 season through the 2003/04 season. HI antibody titers were measured three times in one season: pre-vaccination, post-vaccination, and post-epidemic. To test negative effects of immune response to the repeated vaccination, differences between protection rates and differences between response rates were analyzed for individuals in the two consecutive seasons. For the test of waning effectiveness, we measured the difference in geometric mean titers of HI antibody between post-epidemic results and pre-vaccination results obtained in the following season.
Protection rates were 40-55% in A/New Caledonia/20/99 and ≥75% in A/Panama/2007/99 by repeated vaccination. In A/New Caledonia/20/99 and A/Panama/2007/99 in the 2003/04 season, significant decreases were found in protection rates from the earlier seasons, although the rate for A/Panama/2007/99 in the 2002/03 season increased significantly from that of the prior season. The respective response rates in the 2003/04 season in A/New Caledonia/20/99, and in the 2002/03 and 2003/04 seasons in A/Panama/2007/99 decreased significantly from those of earlier seasons. Regarding waning effectiveness, antibody titers for A/New Caledonia/20/99 in 2003/04 season, and A/Panama/2007/99 in 2002/03 and 2003/04 seasons decreased significantly to 37.0-66.7%.
Results show significant negative effects of immune response by repeated vaccination and show significant waning effectiveness during the interseason for individuals with the same strain of influenza type A. The proportion of elderly people with HI antibody titers of ≥1:40 might be maintained by repeated influenza vaccination.

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