Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18–45 years: Follow-up through Month 48 in a Phase III randomized study

We previously reported higher anti-HPV-16 and - 18immune responses induced by HPV-16/ 18 vaccinecompared with HPV-6/11/16/ 18 vaccineat Month 7 (one month after completion of full vaccinationseries) 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 antibodieswere 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV- 18) in HPV-16/ 18 vaccinegroup than in HPV-6/11/16/ 18 vaccinegroup. The majority of women in both vaccinegroups remained seropositive for HPV-16. The same trend was observed for HPV- 18in HPV-16/ 18 vaccinegroup; however, seropositivity rates in HPV-6/11/16/ 18 vaccinegroup decreased considerably, particularly in the older age groups. In the total vaccinatedcohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and - 18 neutralizing antibodylevels induced by HPV-16/ 18 vaccinewere higher than those induced by HPV-6/11/16/ 18 vaccine. CD4+ T-cell response for HPV-16 and HPV- 18was higher in HPV-16/ 18 vaccinegroup than in HPV-6/11/16/ 18 vaccinegroup. Memory B-cellresponses appeared similar between vaccinegroups. Both vaccineswere generally well tolerated. Overall, the higher immune response observed with the HPV-16/ 18 vaccinewas maintained up to Month 48. A head-to-head study incorporating clinical endpointswould be required to confirm whether the observed differences in immune response between the vaccinesinfluence the duration of protection they provided.