Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women.
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.


CONCLUSIONS
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.
University of California, Division of Adolescent Medicine, San Franscico, CA 94118, USA. moscickia@peds.ucsf.edu
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Moscicki
C M
CM
Wheeler
B
B
Romanowski
J
J
Hedrick
S
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Gall
D
D
Ferris
S
S
Poncelet
T
T
Zahaf
P
P
Moris
B
B
Geeraerts
D
D
Descamps
A
A
Schuind
D000293:Adolescent; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control; D055815:Young Adult
D053918:Papillomavirus Vaccines