Antibody Titers Following the HPV4 Series Administered at Delayed Dosing Intervals

Background: Although HPV4 vaccine is recommended as a 3-dose series administered at 0, 1-2, and 6 months, many do not adhere to this schedule.  Our objective was to assess antibody titers to HPV when 2^nd and/or 3^rd doses of HPV4 are administered either according to recommendations or late.

Methods: Healthy females aged 9-18 years were enrolled at the time of receipt of their 2^nd or 3^rd HPV4.  Participants were assigned to one of four groups depending upon the timing of prior receipt of HPV4: Group 1 – doses 2, 3 on time; Group 2 – only dose 2 late (> 90 days); Group 3 – only dose 3 late (>180 days); and, Group 4 – doses 2, 3 late.  A blood sample was obtained 1 month after the 3^rd HPV4.   HPV antibody (types 6, 11, 16, and 18) was measured using the VLP-IgG ELISA with parallel-line method to determine titers and is expressed as a geometric mean titer (GMT).

Results: Of 331 eligible participants, 286 received a 3^rd HPV4 and had a blood sample.  The median age for Group 3 (14 years) or 4 participants (15 years) was older than that of Group 1 participants (13 years) (p=0.04 and p<0.001, respectively). GMTs were not significantly lower for any of groups who received HPV4 late when compared to the group who received HPV4 as recommended.  GMTs to HPV types 6 and 11 were significantly higher in group 3 versus group 1 (p<0.05 and p=0.02, respectively). 

Conclusions: When compared to girls receiving HPV4 according to the recommended schedule, girls receiving either their 2^nd or 3^rd dose, or both doses, late did not have significantly lower antibody concentrations to any HPV type. These results support current recommendations to not administer additional doses of HPV vaccine for girls who receive the 2^nd or 3^rd HPV4 doses late.