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

Gregory A. Poland, Robert M. Jacobson, Laura A. Koutsky, Gretchen M. Tamms, Radha Railkar, Judith F. Smith, Janine T. Bryan, Paul F. Cavanaugh, Kathrin U. Jansen, Eliav Barr

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Abstract

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.

LanguageEnglish (US)
Pages601-610
Number of pages10
JournalMayo Clinic Proceedings
Volume80
Issue number5
StatePublished - 2005

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Human papillomavirus 16
varespladib methyl
Vaccines
Randomized Controlled Trials
Placebos
Papillomavirus Infections
Capsid Proteins
Serum
Multicenter Studies
Radioimmunoassay
Immunization
Vaccination
Injections
Antibodies

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  • Medicine(all)

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Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16 : A 2-year randomized controlled clinical trial. / Poland, Gregory A.; Jacobson, Robert M.; Koutsky, Laura A.; Tamms, Gretchen M.; Railkar, Radha; Smith, Judith F.; Bryan, Janine T.; Cavanaugh, Paul F.; Jansen, Kathrin U.; Barr, Eliav.

In: Mayo Clinic Proceedings, Vol. 80, No. 5, 2005, p. 601-610.

Research output: Contribution to journalArticle

Poland, GA, Jacobson, RM, Koutsky, LA, Tamms, GM, Railkar, R, Smith, JF, Bryan, JT, Cavanaugh, PF, Jansen, KU & Barr, E 2005, 'Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16: A 2-year randomized controlled clinical trial' Mayo Clinic Proceedings, vol 80, no. 5, pp. 601-610.
Poland, Gregory A. ; Jacobson, Robert M. ; Koutsky, Laura A. ; Tamms, Gretchen M. ; Railkar, Radha ; Smith, Judith F. ; Bryan, Janine T. ; Cavanaugh, Paul F. ; Jansen, Kathrin U. ; Barr, Eliav. / Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16 : A 2-year randomized controlled clinical trial. In: Mayo Clinic Proceedings. 2005 ; Vol. 80, No. 5. pp. 601-610
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abstract = "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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AU - Koutsky,Laura A.

AU - Tamms,Gretchen M.

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AU - Smith,Judith F.

AU - Bryan,Janine T.

AU - Cavanaugh,Paul F.

AU - Jansen,Kathrin U.

AU - Barr,Eliav

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N2 - 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.

AB - 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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