Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals. Issue 6 (1st February 2018)

• Record Type: Journal Article
• Authors: Widdice, Lea E.; Unger, Elizabeth R.; Panicker, Gitika; Hoagland, Rebecca; Callahan, S. Todd; Jackson, Lisa A.; Berry, Andrea A.; Kotloff, Karen; Frey, Sharon E.; Harrison, Christopher J.; Pahud, Barbara A.; Edwards, Kathryn M.; Mulligan, Mark J.; Sudman, Jon; Bernstein, David I.
• Is Part Of: Vaccine. Volume 36:Issue 6(2018)
• Page Start: 881
• Page End: 889
• Publication Date: 2018-02-01
• Subjects: Human papillomavirus -- Vaccine -- Immunity -- Geometric mean titers -- Dosing -- Interval; CI confidence interval -- ELISA enzyme-linked immunosorbent assay -- GMT geometric mean titer -- HPV human papillomavirus -- Log10 logarithmic base 10 -- LS least squares -- 4vHPV quadrivalent human papillomavirus vaccine -- US United States -- VTEU Vaccine and Treatment Evaluation Unit; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.12.042
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Antibody responses in 9–17 year old girls enrolled from community settings were assessed. GMTs after prolonged intervals were non-inferior to recommended intervals. Six-month post-dose 3 GMTs after prolonged intervals were superior to recommended intervals. A prolonged interval between dose 1 and 2 may enhance antibody response. Antibody responses after delayed dose 2 were similar in older and younger girls. Abstract: Background: The 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. Methods: This 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. Results: Compared 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. Conclusions: Prolonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV. ClinicalTrials.gov (NCT00524745 ).