Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination

Abstract

This randomized, partially-blind study (ClinicalTrials.gov registration number NCT00541970) evaluated the immunogenicity and safety of 2-dose (2D) schedules of the HPV-16/18 AS04-adjuvanted vaccine. Results to month (M) 24 have been reported previously and we now report data to M48 focusing on the licensed vaccine formulation (20 μg each of HPV-16 and -18 antigens) administered at M0,6 compared with the standard 3-dose (3D) schedule (M0,1,6). Healthy females (age stratified: 9–14, 15–19, 20–25 years) were randomized to receive 2D at M0,6 (n = 240) or 3D at M0,1,6 (n = 239). In the according-to-protocol immunogenicity cohort, all initially seronegative subjects seroconverted for HPV-16 and -18 antibodies and remained seropositive up to M48. For both HPV-16 and -18, geometric mean antibody titer (GMT) ratios (3D schedule in women aged 15–25 years divided by 2D schedule in girls aged 9–14 years) at M36 and M48 were close to 1, as they were at M7 when non-inferiority was demonstrated. The kinetics of HPV-16, -18, -31, and -45 antibody responses were similar for both groups and HPV-16 and -18 GMTs were substantially higher than natural infection titers. The vaccine had a clinically acceptable safety profile in both groups. In summary, antibody responses to a 2D M0,6 schedule of the licensed vaccine formulation in girls aged 9–14 years appeared comparable to the standard 3D schedule in women aged 15–25 years up to 4 years after first vaccination. A 2D schedule could facilitate implementation of HPV vaccination programs and improve vaccine coverage and series completion rates.

The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model

“…37 Accounting for those who do not complete the vaccine series would necessitate assumptions regarding vaccine efficacy and duration of protection for those who receive only one or 2 doses. [38][39][40] More complex models are better suited than ours for examining issues related to vaccine protection with less than 3 doses. 41 Instead, we used the simplifying assumption of 100% series completion not only to facilitate the use of our simplified model but also to allow for an easier interpretation of our results regarding the cost-effectiveness of 9vHPV compared with 4vHPV.…”

Parents’ decision-making about the human papillomavirus vaccine for their daughters: II. Qualitative results

“…Accordingly, over the course of 5 y (first 2 doses administered in grade 4 and a booster dose first planned but finally not administered, based on a decision by the government of Quebec, in Grade 9), parents may be exposed to other factors in the interim that influence their initial and final decision. However, since there is now evidence to suggest that 2 doses of the HPV vaccine may be sufficient to bolster immunity, 34,35 the province of Quebec has opted to administer 2 doses. 15 Research implication and future directions Future research directions should better address the informational needs of parents not only prior to vaccination, but also following vaccination since parents in our sample seemed to desire more information after having made their decision.…”

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“…Both vaccines are to be administered as a 0.5ml intramuscular injection in the deltoid region from the age of 9 years onwards. Two dose vaccination (0 and 6 months) in girls aged 9 -14 years appeared comparable to the standard 3 dose schedule in women aged 15 -25 years 27 . In the previous study, it clearly shows that only 6.03% women had heard about cervical cancer vaccine 28 .…”