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 μg, 20 μg, 40 μg, or 80 μg 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 μg (n=112),
20 μg (n=105), 40 μg (n=104), or 80 μg (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.
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Article Info
Footnotes
Individual reprints of this article are not available.
This study was funded by Merck Research Laboratories, Rahway, NJ.
Identification
Copyright
© 2005 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
