Seroprotection Rates After Late Doses of Hepatitis B Vaccine

We read with interest the recent article by Middleman et al.1 It shows what we can expect from a clinic-based hepatitis B program targeting adolescents. However, we were quite deluded of the analysis of data. Indeed, several questions emerged after the reading: In Reply—We appreciate the interest and attention with which our article was read by Drs Duval and Deceuninck. They have made some interesting points to which we will respond.Drs Duval and Deceuninck are quite right: antibody titer levels do decay over time. The decline in titer levels, however, is not a simple exponential function of time.2 In fact, titer levels may even rise for some time after a “booster,” and then the titer level decline is initially steep and subsequently flattens. The drop appears steepest during the first 3 months after vaccination.2 Because this first 3 months is the time of greatest titer level flux, we chose to look only at titer levels that were obtained 3 months or more after the last injection of vaccine. This assumes that a more stable titer level has been established that is not changing rapidly after the steeper decline in titer has occurred. The continuous variable of time between the last dose of vaccine and titer level acquisition (the time of titer level acquisition was preset at approximately 12 months after the first dose of vaccine) was not included in the analysis because this time period was dependent on the time between the other injections. Given the extreme level of complexity that this would add to the analysis, the decision was made to assume relative stability of the titer levels 3 months after the latest dose of vaccine.We also agree with the doctors from Québec that the number of unprotected individuals (those who have not achieved seroprotection from the hepatitis B vaccination series) may be overestimated by the figures reported in the paper. Because titer levels may have fallen between vaccination and titer level determination, some individuals in the study who had titer levels below 10 IU/L at 12 months may have achieved seroprotective levels of antibody initially that then declined to below 10 IU/L by the time blood was drawn for the titer level. However, given the way in which adolescents returned for this study, it was not possible to have participants return 2 months after each immunization to establish a standard measurement of titer levels. As one can determine from the subjects’ compliance with the dosing schedule alone, it was unlikely that many would be able to comply with such a strict protocol. Therefore, the seroprotection rates reported reflect the seroprotection rates detectable approximately 12 months after initiation of the vaccination series. In addition, the data do indicate a trend that 2 vaccine doses given close together may not be as effective as 2 doses given further apart in time. This trend is supported by the findings of others.3 Because many of the participants in the study who received the second vaccine dose within a year received the dose 1 month after the first dose (Table 2),4 it is possible that the lower rate of seroprotection noted in the “Results” section is relatively accurate.We appreciate the interest in our paper and the opportunity to discuss this paper further.

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