This suggested that the relative levels of antibodies with high avidity for vaccine-specific HPV strains from Month 7 to 48 were similarly induced in the two-dose recipients to those in the three-dose recipients. At Month 7, 24 or 48, HPV31 L1- or HPV45 L1-specific GM AIs were not different between the two-dose group and the three-dose group (p ≥ 0.311; Fig.

3B). From Month 7 to Month 48, HPV31 L1- or HPV45 L1-specific GM AIs ranged between 0.57–0.60 Selleck LEE011 and 0.56–0.70, respectively, in the two-dose group; and between 0.59–0.61 and 0.54–0.66, respectively, in the three-dose group. This suggested that the relative levels of antibodies with high avidity for non-vaccine-specific but related HPV strains were induced similarly at each period examined (Month 7, 24 and 48) Forskolin clinical trial in the two-dose recipients compared with the three-dose recipients. This exploratory study supplements the observations made in the primary analysis of the HPV-16/18 vaccine clinical trial which demonstrated that the magnitude of antibody responses for the

two-dose schedule (9–14 year olds) was not inferior to the three-dose schedule (15–25 year olds) [6]. Hence the limitations of the present study are that the analyses were post hoc; and, in the comparison of the two-dose versus three-dose schedules, it was assumed that the age of vaccine recipient had no effect on the magnitude of the AI. In the present study, no differences in AIs were observed at Months 7, 24 and 48 between the groups of two-dose and three-dose HPV-16/18 vaccine recipients, suggesting

that the quality of the antibody responses to HPV16, 18, 31 or 45 L1 VLPs in terms of avidity was similar in the two groups. As expected, the AIs for HPV31 L1 and HPV45 L1 VLPs were relatively lower than for HPV16 and 18 L1 VLPs, since these VLPs are not vaccine types and the L1 protein sequence homologies with HPV16 and 18 L1 are 83% and 88%, respectively [27]. Therefore, and in line with what has been proposed with the heptavalent pneumococcal vaccine [28], antibody avidity, in addition to antibody concentration, can be a useful immunological attribute in the evaluation of alternative vaccine others schedules. Antigen-specific avidity has been assessed in other studies of HPV vaccines [9], [10], [19], [20] and [29]. An underlying objective of the present study was to use a methodology that can easily be adopted in the clinical trial setting. Therefore, a single (1 M) concentration of the chaotropic agent NaSCN was selected and antibody concentrations, with and without chaotropic agent, were calculated from serum dilution series. Moreover, ELISA-based assays using a single concentration of chaotropic agent have been reliably used elsewhere to measure the avidity of polyclonal antibodies in human serum samples [18] and [30]. The one-step aspect of the assay may make it more amenable for high-throughput analyses than the two-step ELISA methodology reported by Dauner et al. [20] and [29].