Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals

Publication date: Available online 3 January 2018
Source:Vaccine
Author(s): Lea E. Widdice, Elizabeth R. Unger, Gitika Panicker, Rebecca Hoagland, S. Todd Callahan, Lisa A. Jackson, Andrea A. Berry, Karen Kotloff, Sharon E. Frey, Christopher J. Harrison, Barbara A. Pahud, Kathryn M. Edwards, Mark J. Mulligan, Jon Sudman, David I. Bernstein
BackgroundThe originally recommended dosing schedule, 0, 2, 6 months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2.MethodsThis multi-site, prospective study enrolled healthy 9–17 year old girls (n = 1321) on the day of or within 28 days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age.ResultsCompared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants ≥15 years old had no difference in post-dose 2 titers compared to <15 year olds when dose 2 was substantially delayed.ConclusionsProlonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV.ClinicalTrials.gov (NCT00524745).



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