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

Mark H. Einstein, Myron J. Levin, Archana Chatterjee, Nahida Chakhtoura, Peter Takacs, Grégory Catteau, Francis J. Dessy, Philippe Moris, Lan Lin, Frank Struyf, Gary Dubin, Mark Blatter, Christopher V. Chambers, Marina Fernandez, Bradley Fox, David L. Fried, Sidney A. Funk, Cheryl A. Hansen, James A. Hedrick, Bethany Hoffman & 10 others Terry D. Klein, Jacob Lalezari, Michael J. Noss, James H. Silverblatt, Rhoda S. Sperling, Karen G. Swenson, Troy Thompson, Mark Turner, Michael W. Warren, Robert Yoachim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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. CD4+ 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.

Original languageEnglish (US)
Pages (from-to)3455-3465
Number of pages11
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2014

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Human papillomavirus 11
Human papillomavirus 6
Human papillomavirus 18
Human papillomavirus 16
Vaccines
Safety
Neutralizing Antibodies
DNA

Keywords

  • Cervarix®
  • Gardasil®
  • Human papillomavirus
  • Immunogenicity
  • Safety

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

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. / Einstein, Mark H.; Levin, Myron J.; Chatterjee, Archana; Chakhtoura, Nahida; Takacs, Peter; Catteau, Grégory; Dessy, Francis J.; Moris, Philippe; Lin, Lan; Struyf, Frank; Dubin, Gary; Blatter, Mark; Chambers, Christopher V.; Fernandez, Marina; Fox, Bradley; Fried, David L.; Funk, Sidney A.; Hansen, Cheryl A.; Hedrick, James A.; Hoffman, Bethany; Klein, Terry D.; Lalezari, Jacob; Noss, Michael J.; Silverblatt, James H.; Sperling, Rhoda S.; Swenson, Karen G.; Thompson, Troy; Turner, Mark; Warren, Michael W.; Yoachim, Robert.

In: Human Vaccines and Immunotherapeutics, Vol. 10, No. 12, 01.12.2014, p. 3455-3465.

Research output: Contribution to journalArticle

Einstein, MH, Levin, MJ, Chatterjee, A, Chakhtoura, N, Takacs, P, Catteau, G, Dessy, FJ, Moris, P, Lin, L, Struyf, F, Dubin, G, Blatter, M, Chambers, CV, Fernandez, M, Fox, B, Fried, DL, Funk, SA, Hansen, CA, Hedrick, JA, Hoffman, B, Klein, TD, Lalezari, J, Noss, MJ, Silverblatt, JH, Sperling, RS, Swenson, KG, Thompson, T, Turner, M, Warren, MW & Yoachim, R 2014, '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', Human Vaccines and Immunotherapeutics, vol. 10, no. 12, pp. 3455-3465. https://doi.org/10.4161/hv.36117
Einstein, Mark H. ; Levin, Myron J. ; Chatterjee, Archana ; Chakhtoura, Nahida ; Takacs, Peter ; Catteau, Grégory ; Dessy, Francis J. ; Moris, Philippe ; Lin, Lan ; Struyf, Frank ; Dubin, Gary ; Blatter, Mark ; Chambers, Christopher V. ; Fernandez, Marina ; Fox, Bradley ; Fried, David L. ; Funk, Sidney A. ; Hansen, Cheryl A. ; Hedrick, James A. ; Hoffman, Bethany ; Klein, Terry D. ; Lalezari, Jacob ; Noss, Michael J. ; Silverblatt, James H. ; Sperling, Rhoda S. ; Swenson, Karen G. ; Thompson, Troy ; Turner, Mark ; Warren, Michael W. ; Yoachim, Robert. / 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. In: Human Vaccines and Immunotherapeutics. 2014 ; Vol. 10, No. 12. pp. 3455-3465.
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abstract = "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. CD4+ 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.",
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T1 - 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

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AU - Einstein, Mark H.

AU - Levin, Myron J.

AU - Chatterjee, Archana

AU - Chakhtoura, Nahida

AU - Takacs, Peter

AU - Catteau, Grégory

AU - Dessy, Francis J.

AU - Moris, Philippe

AU - Lin, Lan

AU - Struyf, Frank

AU - Dubin, Gary

AU - Blatter, Mark

AU - Chambers, Christopher V.

AU - Fernandez, Marina

AU - Fox, Bradley

AU - Fried, David L.

AU - Funk, Sidney A.

AU - Hansen, Cheryl A.

AU - Hedrick, James A.

AU - Hoffman, Bethany

AU - Klein, Terry D.

AU - Lalezari, Jacob

AU - Noss, Michael J.

AU - Silverblatt, James H.

AU - Sperling, Rhoda S.

AU - Swenson, Karen G.

AU - Thompson, Troy

AU - Turner, Mark

AU - Warren, Michael W.

AU - Yoachim, Robert

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KW - Cervarix®

KW - Gardasil®

KW - Human papillomavirus

KW - Immunogenicity

KW - Safety

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