Long intervals between two doses of HPV vaccines and magnitude of the immune response: a post hoc analysis of two clinical trials

Abstract

The objective of this analysis was to compare the anti-HPV GMTs and their distribution after a 6-month or a 3-8-y interval between two HPV vaccine doses. The results from two clinical trials, conducted by the same team in the same region, with serological assays performed at the same laboratory using the same ELISA methodology were compared. In the first study, 173 9-10-y-old girls and boys received two doses of 9vHPV vaccine at a 6-month interval; in the second study, 31 girls vaccinated with one dose of 4vHPV at the age of 9-14 y received a dose of 9vHPV 3-8 y later (mean 5.4 y). In both studies, blood samples were collected before and 1 month post second dose. Despite large differences in the time since the first dose, all subjects (100%) were seropositive to the common 4 HPV types (6, 11, 16 and 18) to both vaccines, with comparable GMTs and titer distributions before the second dose. One month post second dose, the GMTs increased 40-91-fold for those with a 6-month interval between doses and 60-82-fold for those with a 3-8-y interval. Titer distributions after the booster dose were comparable in the two studies. These results indicate that 2-dose HPV vaccination schedules with an interval of several years could be used for pre-adolescents. Intervals longer than 6 months may facilitate logistics for immunization programs and could be useful during periods of vaccine shortage or as a transition while the effectiveness of a one-dose schedule is being evaluated.

Is one dose of human papillomavirus vaccine as effective as three?: A national cohort analysis

“…Analyses with more follow–up time will be undertaken, as will analyses including only girls vaccinated at 12–13 years. Recent data supports both the immunogenicity of one dose of quadrivalent vaccine given routinely to 9–14 year olds and the strong response to boosting achievable 3–8 years later using a dose of nonavalent HPV vaccine, supporting that a booster dose would be effective, if trial data or long term follow up data indicated it was required, for cohorts who had been given one dose [34]. There is a strong and successful precedent for trial implementation of reduced dose schedules with HPV vaccines, with both Quebec and Mexico initially implementing a two–dose schedule with a third ‘booster’ dose scheduled years later if needed (not required to date) [35].…”

Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis

“…To our knowledge, the only study that has examined this interval found that extended intervals resulted in similar levels of geometric mean IgG antibody titres when the second dose was given 6 months or 3-8 years after the first dose. 40 Finally, WHO recommended that countries consider routine vaccination of girls aged 9 years with a 3-5 year extended interval between doses (with a catch-up programme at age 14 years) after careful consideration of its programmatic challenges, and with a clear and well planned communication strategy. 10 Our study has five major strengths.…”

Continued HPV vaccination in the face of unexpected challenges: A commentary on the rationale for an extended interval two-dose schedule

“…Further evidence (identified through our own scoping review, conducted in MEDLINE, of evidence published since September 2018) comes from a post-hoc analysis of two intervention studies conducted in Canada (Table 1; #5) [8]. HPV16/18 GMTs were not significantly different post-vaccination in groups with a 6-month versus 3-8-year dosing interval.…”