Influenza vaccine dosages

Drs. Couch et al. have recently published a randomized vaccination trial in ambulatory elderly assessing reactogenicity and antibody response to inactivated trivalent influenza vaccine with dosages of either 15g (standard) or 60 g hemagglutinin (HA) per strain [1]. They rightly state that the ‘‘dose—response relationship for serum antibody responses in humans to increased dosage of inactivated influenza vaccine antigens is well established’’. Ideally, the relationship between increasing vaccine doses and serum antibody titers is described by a sigmoid dose—response curve (Fig. 1).
The curve shows that any increase in dose is associated with an increase in antibody titer. However, due to the sigmoid shape of the curve, the increase in antibody titer is not constant, but depends on dose. In the hatched area of the curve, small dose changes are associated with dramatically large titer increases, whereas in the crosshatched area, even very large dose increases hardly improve the antibody response. The data presented by Couch et al. suggest that their dose interval (15—60 g HA) is located predominantly in the crosshatched area rather than in the hatched area, as the titer means for the 60 g dose is only 1.2—1.7-fold larger than those for the 15 g dose (Table 1). Almost 20 years ago, we performed a similar dose—response trial in the elderly (nursing home residents), which was published in Vaccine [2] in 1993. Despite a different sensitivity of the antibody assay used (resulting in absolutely larger titers) and a slightly different dose of the standard vaccine (10 g HA per strain), the ratios high/standard dose were remarkably similar to the results of Couch et al. for the influenza A strains, and only somewhat larger for the B strain.
In 1993, we regarded the antibody increase associated with the 60g dose too small to overcome the well established impairment of the humoral immunity in the elderly and concluded that ‘‘increasing the vaccine dose is no adequate method to improve the antibody response’’. In 2007, Couch et al. concluded from similar results that a high-dose vaccine could be a promising strategy in the elderly. May be a formal meta-analysis of all published dose—response data could contribute to further clarify this issue.