In a phase III randomized trial, 2 doses of quadrivalent HPV (HPV-4) given to 9-13 year old girls (0,6months (M)) was non-inferior to 3 doses given to 16-26 year old women (0,2,6M). In the original trial, we also included a 3 dose arm for girls 9-13 year old (0,2,6M). In this study, we report the 60M follow up after first dose for the 2- and 3-dose girls.
Participants provided a blood sample at 60M. Sera were evaluated using Merck Competitive Luminex ImmunoAssay (cLIA) and total IgG LIA (Luminex Immunoassay) assays to assess serum antibodies to HPV-6,11,16 and 18. Seropositivity (SP) rates and geometric mean titre (GMT) for genotypes were compared between 2- and 3-dose recipients. The 2-sample t-test with unequal variances was used to compute p-values.
101 girls provided blood samples (50:2 dose;51:3 dose group). With the exception of HPV-18, seropositivity was >95% for other genotypes. There was no significant difference in seropositivity between 2 and 3 dose girls. There was no significant difference in GMTs using IgG or cLIA between 2- and 3-dose recipients with the exception of HPV-18 cLIA (p=0.04).
| Type | Assay | 2 Dose SP % (95%CI) | 3 Dose SP % (95%CI) | 2 Dose GMT* (95%CI) | 3 Dose GMT*(95%CI) |
| 6 | cLIA | 96 (86-100) | 98 (90-100) | 150 (114-198) | 205 (157-269) |
| 6 | IgG | 100 (93-100) | 100 (93-100) | 207 (147-291) | 242 (180-327) |
| 11 | cLIA | 100 (93-100) | 100 (93-100) | 223 (167-298) | 225 (174-289) |
| 11 | IgG | 98 (89-100) | 98 (90-100) | 163 (120-220) | 170 (125-230) |
| 16 | cLIA | 100(93-100) | 100 (93-100) | 949 (691-1304) | 829 (628-1094) |
| 16 | IgG | 100 (93-100) | 100 (93-100) | 904 (668-1223) | 735 (541-998) |
| 18 | cLIA | 84 (71-93) | 94 (84-99) | 78 (53-117) | 137 (94-198) |
| 18 | IgG | 86 (73-94) | 92 (81-98) | 107 (73-158) | 143 (99-204) |
*GMT for cLIA and LIA is expressed as milli Merck Units/ml
At 60M post dose 1, there was no significant difference in SP or GMTs between 2- and 3-doses girls ages 9-13 year, with the exception of HPV-18 cLIA GMTs. HPV-18 IgG GMTs however, were not significantly different. 2- and 3-dose SP remains relatively unchanged from the 36M rates in these groups (data not shown). This analysis provides reassurance for programs using 2 doses HPV-4 that immunogenicity is comparable to 3-doses at 60M after dose 1. These study participants are also a subgroup of a larger cohort under evaluation for effectiveness of the 2-dose HPV-4 vaccine, which will provide further guidance regarding the impact of reduced dose schedules.