TY - JOUR
T1 - Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women
AU - Moscicki, A. B.
AU - Wheeler, C. M.
AU - Romanowski, B.
AU - Hedrick, J.
AU - Gall, S.
AU - Ferris, D.
AU - Poncelet, S.
AU - Zahaf, T.
AU - Moris, P.
AU - Geeraerts, B.
AU - Descamps, D.
AU - Schuind, A.
N1 - Funding Information:
Contributors: All authors have made substantial contribution to the conception and design of the study, or acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and have approved the submitted version of the article. Conflicts of interest statement: Institutions of A.B. Moscicki, C.M. Wheeler, B. Romanowski, J. Hedrick, S. Gall and D. Ferris received support from GlaxoSmithKline Vaccines to conduct this study and/or other HPV vaccine studies. C.M. Wheeler received support from Merck and Co., Inc. through the University of New Mexico to conduct HPV vaccine studies. B. Romanowski received consulting fee/honorarium from GlaxoSmithKline Vaccines. A.B. Moscicki and C.M. Wheeler received support for travel to meetings from GlaxoSmithKline Vaccines. B. Romanowski received fees for participation in advisory boards, lectures and for development of educational presentations from GlaxoSmithKline Vaccines. Through the University of New Mexico, C.M. Wheeler received equipment and reagents for HPV genotyping from Roche Molecular Systems. S. Poncelet, T. Zahaf, P. Moris, B. Geeraerts, D. Descamps and A. Schuind are employees of GlaxoSmithKline Vaccines. P. Moris, D. Descamps and A. Schuind hold stock options from GlaxoSmithKline Vaccines.
PY - 2012/12/17
Y1 - 2012/12/17
N2 - Background: Vaccines are now available for the prevention of HPV-16/18-related cervical infections and pre-cancers, primarily targeting adolescent girls. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine-derived immunity should be long-term. The current study, HPV-024 (NCT00546078, http://clinicaltrials.gov), assessed the immune memory in North American women who received three doses of HPV-16/18 AS04-adjuvanted vaccine 7 years earlier in HPV-001 (NCT00689741). Methods: Women vaccinated in HPV-001 received a 4th-dose of the HPV-16/18 vaccine (024-4DV group, N=65). Post 4th-dose immune responses were compared with post 1st-dose immune responses in cross-vaccination controls (024-3DV group, N=50). Reactogenicity was compared between the 4th-dose and the 1st-dose administration. Results: Pre 4th-dose, 100% of subjects in the 024-4DV group remained seropositive for anti-HPV-16/18 antibodies (ELISA). Compared to pre 4th-dose, GMTs for anti-HPV-16 and anti-HPV-18 antibodies were respectively 9.3-fold and 8.7-fold higher at day 7, and 22.7-fold and 17.2-fold higher at month 1. Compared to post 1st-dose, GMTs for anti-HPV-16 and anti-HPV-18 were respectively 80.5-fold and 205.4-fold higher at day 7, and 11.8-fold and 20.5-fold higher at month 1. Furthermore, 68.2% and 77.3% of women had HPV-16/18 specific memory B-cells, respectively, pre 4th-dose, rising to 100% one month post 4th-dose vaccination. The 4th-dose was generally well tolerated. Conclusion: A 4th-dose of HPV-16/18 AS04-adjuvanted vaccine triggered a rapid and strong anamnestic response in previously vaccinated women, demonstrating vaccine-induced immune memory.
AB - Background: Vaccines are now available for the prevention of HPV-16/18-related cervical infections and pre-cancers, primarily targeting adolescent girls. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine-derived immunity should be long-term. The current study, HPV-024 (NCT00546078, http://clinicaltrials.gov), assessed the immune memory in North American women who received three doses of HPV-16/18 AS04-adjuvanted vaccine 7 years earlier in HPV-001 (NCT00689741). Methods: Women vaccinated in HPV-001 received a 4th-dose of the HPV-16/18 vaccine (024-4DV group, N=65). Post 4th-dose immune responses were compared with post 1st-dose immune responses in cross-vaccination controls (024-3DV group, N=50). Reactogenicity was compared between the 4th-dose and the 1st-dose administration. Results: Pre 4th-dose, 100% of subjects in the 024-4DV group remained seropositive for anti-HPV-16/18 antibodies (ELISA). Compared to pre 4th-dose, GMTs for anti-HPV-16 and anti-HPV-18 antibodies were respectively 9.3-fold and 8.7-fold higher at day 7, and 22.7-fold and 17.2-fold higher at month 1. Compared to post 1st-dose, GMTs for anti-HPV-16 and anti-HPV-18 were respectively 80.5-fold and 205.4-fold higher at day 7, and 11.8-fold and 20.5-fold higher at month 1. Furthermore, 68.2% and 77.3% of women had HPV-16/18 specific memory B-cells, respectively, pre 4th-dose, rising to 100% one month post 4th-dose vaccination. The 4th-dose was generally well tolerated. Conclusion: A 4th-dose of HPV-16/18 AS04-adjuvanted vaccine triggered a rapid and strong anamnestic response in previously vaccinated women, demonstrating vaccine-induced immune memory.
KW - Anamnestic response
KW - Cervical cancer
KW - HPV infection
KW - HPV vaccine
KW - Sustained immunity
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U2 - 10.1016/j.vaccine.2012.09.037
DO - 10.1016/j.vaccine.2012.09.037
M3 - Article
C2 - 23063422
AN - SCOPUS:84870532430
SN - 0264-410X
VL - 31
SP - 234
EP - 241
JO - Vaccine
JF - Vaccine
IS - 1
ER -
