Abbreviations: ANOVA, analysis of variance; AS04, Adjuvant System containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL; 50 mg) adsorbed on aluminum salt (500 mg Al(OH) 3 ); ATP, according-to-protocol; CI, confidence interval; CMI, cell-mediated immune; CVS, cervicovaginal secretion; ED 50 , effective dose producing 50% response; ELISA, enzyme-linked immunosorbent assay; GM, geometric mean; GMR, geometric mean (titer) ratio; GMT, geometric mean titer; HPA, Health Protection Agency; HPV, human papillomavirus; IgG, immunoglobulin G; MSC, medically significant condition; nAb(s), neutralizing antibody(ies); NOAD, new onset autoimmune disease; NOCD, new onset chronic disease; PBMC, peripheral blood mononuclear cells; PBNA, pseudovirion-based neutralization assay; SAE, serious adverse event; TVC, total vaccinated cohort; VLP, virus-like particle.We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0-to 5.2-fold higher (HPV-16) and 8.6-to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/ 11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4C T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.
