Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16: a 2-year randomized controlled clinical trial.

OBJECTIVE: To evaluate the immunogenicity, reactogenicity, and tolerability of a prototype human papillomavirus (HPV) 16 viruslike particle (VLP) vaccine directed against the L1 capsid protein. SUBJECTS AND METHODS: We enrolled healthy nonpregnant women aged 18 to 26 years into a 2-year, double-blind, dose-ranging multicenter trial (October 12, 1998, to September 30, 2001). Subjects were assigned to study groups to receive a 3-dose regimen (day 0, month 2, and month 6) of 1 of 4 vaccine doses: 10 microg, 20 microg, 40 microg, or 80 microg or placebo. Serum anti-HPV 16 L1 antibody (sL1Ab) geometric mean titers (GMTs) were measured at day 0, at month 3, at month 7, and every 6 months for a total of 2 years using a radioimmunoassay. The primary immunogenicity analyses evaluated GMTs at month 7 in L1Ab-seronegative subjects at baseline. Vaccine tolerability was also assessed. RESULTS: A total of 480 subjects were randomized to receive placebo (n=52) or 10 microg (n=112), 20 microg (n=105), 40 microg (n=104), or 80 microg (n=107) of HPV 16 L1 VLP vaccine. At baseline, 75% of subjects were L1Ab seronegative. All vaccine doses produced a statistically significant sL1Ab response vs placebo (P<.001). At the completion of the vaccination regimen, sL1Ab GMTs in baseline-seronegative subjects were 36- to 78-fold higher than the sL1Ab GMT at day 0 observed in subjects who had mounted an immune response to HPV 16 infection before enrollment. Serum L1Ab GMTs remained high throughout the 1.5-year postvaccination period. Postvaccination sL1Ab GMTs were 1.1- to 2.4-fold higher in women who had detectable sL1Ab levels at enrollment compared with those in baseline-seronegative subjects, particularly in the persistence phase. The vaccine was generally well tolerated with no statistically significant differences in injection site or systemic adverse experiences among treatment groups. CONCLUSION: Immunization with this novel HPV 16 L1 VLP vaccine was well tolerated and produced an immunogenic response that persisted for at least 1.5 years after the final dose.